Opinion
Index No. 2499/2014
04-15-2020
Jennifer LIESE, Plaintiff, v. William HENNESSEY and Merle Hennessey, Defendants.
For Plaintiff: Jonathan R. Goldman, Esq., Sussman and Associates, Goshen, NY For Defendant: Henry L. Liao, Esq., Penino & Moynihan, LLP, White Plains, NY
For Plaintiff: Jonathan R. Goldman, Esq., Sussman and Associates, Goshen, NY
For Defendant: Henry L. Liao, Esq., Penino & Moynihan, LLP, White Plains, NY
Catherine M. Bartlett, J.
The following papers numbered 1 to 9 were read on Defendants' application to preclude the proposed testimony of Plaintiff's expert, Dr. Irene Grant:
Transcripts of Hearing Testimony (4/1, 4/23, 4/24, 5/17, 6/17 of 2019) ... 1-5
Hearing Exhibits ... 6
Plaintiff's Post-Frye Hearing Brief ... 7
Defendants' Response to Plaintiff's Post-Frye Hearing Brief ... 8
Plaintiff's Post-Frye Hearing Reply Brief ... 9
Upon the foregoing papers, it is ORDERED that Defendants' application is determined as follows:
I. INTRODUCTION
Plaintiff Jennifer Liese commenced this action on April 2, 2014 to recover for injuries allegedly sustained due to exposure to molds and mold by-products on premises, leased from defendants William and Merle Hennessey, where she resided for approximately five months from mid-December 2010 to early May 2011. Plaintiff's infectious disease expert, Irene Grant, M.D., who was one of her treating physicians, proposes to testify that as a result of alleged exposure to mold on Defendants' premises Plaintiff suffered injuries as set forth in her Bill of Particulars, including "invasive fungal infection ; respiratory disease; permanent fibrotic and scarring tissue damage in both respiratory and neurologic systems; immunosuppression with increased susceptibility to infection, hemorrhage, necrosis of tissues and possible death; cognitive impairment; gait disturbance; sinus congestion / sinusitis ; shortness of breath and dyspnea; reactive airway disease; permanent asthmatic type hyper airway disease; respiratory neuromuscular weakness; ataxia; and numbness."
Defendants moved pursuant to Frye v. United States, 293 F. 1013 (D.C. Cir. 1923), Parker v. Mobil Oil Corp., 7 NY3d 434 (2006), and Cornell v. 360 West 51st Street Realty, LLC, 22 NY3d 762 (2014) to preclude Dr. Grant's testimony on the grounds that:
(1) It is not generally accepted by the relevant scientific / medical community that inhalation in a residential environment of the types of molds and mycotoxins to which Plaintiff was allegedly exposed can cause the illnesses alleged by Plaintiff in humans.
(2) The method by which Dr. Grant attributed Plaintiff's medical conditions to the alleged mold exposure is not generally accepted as reliable by the relevant scientific / medical community.
(3) Assuming arguendo that Dr. Grant employed generally accepted principles and methods, her opinion should nevertheless be excluded based on the "analytical gap between the data and the opinion proffered."
The Court conducted a hearing addressed to the issues of general causation and specific causation (See, Tr. April 1, 2019, pp. 3-6) in five sessions from April 1 to June 17, 2019.
II. THE APPLICABLE LEGAL STANDARDS
A. Frye v. United States : The "General Acceptance" Standard
"Under the Frye standard, expert testimony is admissible only if a scientific ‘principle or procedure has gained general acceptance’ in its specified field ( People v. Wesley, 83 NY2d 417, 422...[1994], quoting Frye v. United States, 293 F. 1013, 1014 [D.C. Cir. 1923] ). People v. Brooks, 31 NY3d 939, 941 (2018)." The burden of proving general acceptance rests upon the party offering the disputed expert testimony." Dovberg v. Laubach, 154 AD3d 810, 813 (2d Dept. 2017). "General acceptance can be demonstrated through scientific or legal writings, judicial opinions, or expert opinions other than that of the proffered expert." Id. ; Shah v. Rahman, 167 AD3d 671, 672 (2d Dept. 2018). However, "[b]road statements of general scientific acceptance, without accompanying support, are insufficient to meet the burden of establishing such acceptance." Id. (quoting Saulpaugh v. Krafte, 5 AD3d 934, 935-936 ).
B. The Frye Standard As Applied To "General Causation"
In Cornell v. 360 West 51st Street Realty, LLC, supra , the Court of Appeals issued a highly detailed opinion concerning the application of Frye to the very issue presented in the case at bar, i.e., injury allegedly caused by exposure to mold in a residential setting. Inasmuch as the Court of Appeals expressly held that the Appellate Division had "improperly applied a modified version of the Frye test to deem [Cornell's] expert's testimony regarding general causation admissible" ( Id., 22 NY3d at 781 ), Cornell is highly probative of the nature of the showing required here to demonstrate general acceptance by the relevant scientific / medical community of the theory of general causation advanced by Plaintiff here.
More specifically, the Court of Appeals concluded that the Appellate Division had erred in deeming the Frye standard satisfied because Ms. Cornell's expert's opinions relating her condition to the mold infestation find "some support in existing data, studies and literature." Id., 22 NY3d at 779 (italics added by Court of Appeals). The literature on which Cornell's expert relied spoke only in terms of "risk", "linkage" or "association", and not "causation."
The Court of Appeals explained why such support does not satisfy Frye :
...Indeed, Dr. Johanning repeatedly equated association with causation. In so doing, he departed from the generally accepted methodology for evaluating epidemiologic evidence when determining whether exposure to an agent causes a harmful effect or disease.
As summarized in the federal courts' Reference Manual on Scientific Evidence:
"Epidemiologists are ultimately interested in whether a causal relationship exists between an agent and a disease. However, the first question an epidemiologist addresses is whether an association exists between exposure to the agent and disease. An association between exposure to an agent and disease exists when they occur together more frequently than one would expect by chance. Although a causal relationship is one possible explanation for an observed association between an exposure and a disease, an association does not necessarily mean that there is a cause-effect relationship. " [cit.om.; italics added by Court of Appeals]
Thus, studies that show an association between a damp and moldy indoor environment and the medical conditions that Dr. Johanning attributes to Cornell's exposure to mold (bronchial-asthma, rhino-sinusitis, hypersensitivity reactions and irritation reactions of the skin and mucous membranes) do not establish that the relevant scientific community generally accepts that molds cause these adverse health effects. But such studies necessarily furnish "some support" for causation since there can be no causation without an association (although, as explained, there can be an association without causation). For these reasons, the Appellate Division was incorrect when it ruled that the Frye standard was satisfied in this case because Dr. Johanning's opinions as to general causation find "some support" in the record. In sum, then, Cornell has not raised a triable issue of fact with respect to general causation.
Id. , at 783 (italics added by Court of Appeals).
Thus, Cornell unequivocally holds that general acceptance per Frye of a theory of general causation may not be established with scientific evidence that speaks only of "risk", "linkage" or "association", and does not go further and demonstrate a cause and effect relationship between the alleged exposure to mold and the plaintiff's illness. Moreover, in the wake of Cornell , the Court of Appeals has reaffirmed that the mere existence of some scientific support in the record is insufficient to establish "general acceptance" under Frye . The proponent's burden is to establish a "consensus in the scientific community." See, People v. Williams, 2020 WL 1516488 at *6 (March 31, 2020) ; Sean R. ex rel Debra R. v. BMW of North America, LLC, 26 NY3d 801, 809 (2016).
C. Parker v. Mobil Oil Corp. : "Specific Causation"
In Parker v. Mobil Oil Corp., 7 NY3d 434 (2006), the Court of Appeals distinguished between the Frye inquiry and "the admissibility question applied to all evidence — whether there is a proper foundation — to determine whether the accepted methods were appropriately employed in a particular case.... ‘The focus moves from the general reliability concerns of Frye to the specific reliability of the procedures followed to generate the evidence proffered and whether they establish a foundation for the reception of the evidence at trial’." Id. , 7 NY3d at 447 (quoting People v. Wesley, supra, 83 NY2d at 429 ).
With regard to the issue here -- causation of injury by exposure to a toxin — the Court wrote:
It is well established that an opinion on causation should set forth a plaintiff's exposure to a toxin, that the toxin is capable of causing the particular illness (general causation) and that plaintiff was exposed to sufficient levels of the toxin to cause the illness (specific causation) [cit.om.]....it is not always necessary for a plaintiff to quantify exposure levels precisely or use the dose-response relationship, provided that whatever methods an expert uses to establish causation are generally accepted in the scientific community.
....
There could be several other ways an expert might demonstrate causation. For instance, amici note that the intensity of exposure to benzene may be more important than a cumulative dose for determining the risk of developing leukemia. Moreover, exposure can be estimated through the use of mathematical modeling by taking a plaintiff's work history into account to estimate the exposure to a toxin. It is also possible that more qualitative means could be used to express a plaintiff's exposure. Comparison to the exposure levels of subjects of other studies could be helpful provided that the expert made a specific comparison sufficient to show how the plaintiff's exposure level related to those of the other subjects. These, along with others, could be potentially acceptable ways to demonstrate causation if they were found to be generally accepted as reliable in the scientific community.
Id. , at 448.
D. The Requirement That An Exposure Sufficient To Demonstrate Specific Causation Be Established By Generally Accepted Methods
Parker's requirement that the plaintiff's exposure to sufficient levels of a toxin to cause illness be demonstrated by methods generally accepted as reliable in the scientific community was elucidated by the Court of Appeals in Cornell, supra, and in Sean R. v. BMW of North America, LLC, 26 NY3d 801 (2016). In Sean R. the Court wrote:
In toxic tort cases, an expert opinion on causation must set forth (1) a plaintiff's exposure to a toxin, (2) that the toxin is capable of causing the particular injuries plaintiff suffered (general causation) and (3) that the plaintiff was exposed to sufficient levels of the toxin to cause such injuries (specific causation) [citing Parker, supra ]. Although it is "not always necessary for a plaintiff to quantify exposure levels precisely" (id. ), we have never "dispensed with a plaintiff's burden to establish sufficient exposure to a substance to cause the claimed adverse health effect" [citing Cornell, supra, 22 NY3d at 784 ]. "At a minimum,...there must be evidence from which the factfinder can conclude that the plaintiff was exposed to levels of the agent that are known to cause the kind of harm that the plaintiff claims to have suffered" [citing Cornell, supra ].
Not only is it necessary for a causation expert to establish that the plaintiff was exposed to sufficient levels of a toxin to have caused his injuries, but the expert also must do so through methods "found to be generally accepted as reliable in the scientific community"
( Parker, 7 NY3d at 449...). This "general acceptance" requirement, also known as the Frye test, governs the admissibility of expert testimony in New York. It asks "whether the accepted techniques, when properly performed, generate results accepted as reliable within the scientific community generally" ( People v. Wesley, 83 NY2d 417, 422...).
Although unanimity is not required, the proponent must show "consensus in the scientific community as to [the methodology's] reliability" ( id., at 439...).
Sean R. v. BMW of North America, LLC, supra , 26 NY3d at 808-809 ).
In Sean R., the causation expert opined that the plaintiff was exposed to a sufficient amount of gasoline vapor to have caused his injuries based on evidence that the smell of gasoline occasionally caused symptoms of dizziness, headaches and throat irritation. She asserted that it was an accepted practice in occupational medicine to use controlled studies of symptoms as a guide when assessing exposures retrospectively. Id., 26 NY3d at 809. The Court of Appeals observed:
We don't disagree with the scientific validity of controlled studies or their ability to measure symptoms in response to a given exposure. But those controlled studies do not support the inverse approach Dr. Frazier employed in this case — working backwards from reported symptoms to divine an otherwise unknown concentration of gasoline vapor. Dr. Frazier has not identified on this record any study, report, article or opinion that admits or employs such a methodology.
Id., at 810. The Court accordingly held that the expert's opinion on causation was properly excluded. Id., at 809, 812.
As the Court of Appeals explained in People v. Brooks, supra, this foundational inquiry ultimately boils down to a question whether "there is simply too great an analytical gap between the data and the opinion proffered" ( id. , 31 NY3d at 941 [quoting Cornell, supra , 22 NY3d at 781 ]; or, otherwise expressed, "whether the expert's opinion sufficiently relates to existing data or ‘is connected to existing data only by the ipse dixit of the expert’." Id. [quoting General Electric Co. v. Joiner, 522 US 136, 146 (1997) ].
III. THE FRYE HEARING
A. Plaintiff's Claims
Plaintiff Jennifer Liese ("JL") alleges that she became severely ill after being exposed to dangerously high levels of mold and its toxic byproducts, called "mycotoxins," while residing in a basement apartment she rented from Defendants between December 2010 and May 2011. Her treating infectious disease specialist, Dr. Irene Grant, opines that as a result of her exposure JL developed a chronic fungal infection -- specifically chronic aspergillosis -- and related respiratory ailments. Dr. Grant opines further that this exposure has suppressed JL's immune system and caused her certain neurological impairments, including recurrent tremors and gait disturbance. (B. 1)
References preceded by "B." are to Plaintiff's PostFrye Hearing Brief. Those preceded by "RB." are to Plaintiff's PostFrye Hearing Reply Brief. Those preceded by "IG" are to the hearing testimony of Dr. Irene Grant. Those preceded by "MP" are to the hearing testimony of Dr. Michael Phillips.
Based on Dr. Grant's opinion, Plaintiff claims that:
(1) Upon moving in to the contaminated basement apartment, JL began inhaling trichothecenes produced by Stachybotrys mold, which damaged her nasal and sinus mucosa, which was already irritated due to prior surgeries, and also damaged the mucosa in her lower airway;
(2) This damage to JL's barrier defense system left her more susceptible to infection from the overloaded presence of Aspergillus ("ASP"), a highly pathogenic mold species;
(3) Over the course of the next five months, while living and strenuously exercising in this environment, thus increasing her respiration of these fungal agents, inhalation of trichothecenes further damaged JL's immune and neural cells and ASP colonized and infected her sinuses;
(4) The partial antifungal treatment and switch of treatment to antibiotics and steroids caused the ASP infection to rapidly progress and spread throughout her upper and lower respiratory tract, developing into a chronic condition;
(5) The continued presence of, and infection by, ASP has resulted in further immune deficiency and neurological impairment due to the production of mycotoxins by the ASP during its infectious state. (B. Par. 47)
In reply to Defendants' showing, Plaintiff claims that JL's inhalation of mycotoxins while living on Defendants' premises is significant as a contributing factor to the breakdown of her barrier defense system, facilitating the mold infiltration and infection, as well as her initial cognitive and neurological symptoms. She attributes the remainder of JL's overall health impairments, and their development over time, to the chronic ASP infection she developed and the mold's production of mycotoxins inside her body during its infectious state. (RB. 1)
B. AAAAI Position Statement (2006) on The Medical Effects of Mold Exposure
In Cornell , the Court of Appeals effectively held that the AAAAI Position Statement on The Medical of Effects Mold Exposure (2006) reflected the general consensus of allergists, immunologists and occupational / environmental physicians and scientists, as of 2008, with respect to mold-induced human illness. Dr. Grant's theory of causation is wholly at odds with the general consensus reflected in the AAAAI paper, which states inter alia that:
Since mold is ubiquitous inside and outside, predisposing host factors in the patient (eg, immunodeficiency disorders ) are the critical factor in the development of opportunistic mold infection. (328) Immunocompetent individuals, even with intense occupational mold exposure, do not manifest opportunistic infection or immunodeficiency. (330)
Mycotoxin-mediated disease does not occur through inhalation in nonoccupational settings. (329)
Exposure to molds and their byproducts does not induce a state of immune dysregulation. (330)
The pertinent passages of the AAAAI Position Statement (326-332) are as follows:
MECHANISM OF INJURY
Exposure to certain fungi (molds) can cause human illness. Molds cause adverse human health effects through 3 specific mechanisms: generation of a harmful immune response (eg, allergy or hypersensitivity pneumonitis [HP] ), direct infection by the organism, and toxic-irritant effects from mold byproducts. For each of these defined pathophysiologic mechanisms, there are scientifically documented mold-related human diseases that present with objective clinical evidence of disease. (326)
ALLERGIC FUNGAL SINUSITIS
Allergic fungal sinusitis is similar to allergic bronchopulmonary aspergillosis in that it is sensitization to multiple allergens, including the fungus implicated in the affected sinus. Criteria for this condition have been well delineated, and it is generally readily distinguishable from typical chronic sinusitis. Specific criteria for diagnosis include eosinophilic a localized hypersensitivity condition resulting from fungal growth in an area of abnormal tissue drainage. Although originally attributed primarily to A fumigatus, other fungi, particularly mitosporic...fungi are more commonly implicated... Almost uniformly there is allergicmucus demonstrating non-invasive fungi, type 1 hypersensitivity (history, positive skin test result, or positive in vitro test result to allergens), nasal polyposis, and characteristic radiographic findings. (327)
INFECTION
Individuals with recognized primary and secondary immunodeficiency disorders are at increased risk for infection with a wide range of opportunistic fungi, with the risk varying with the degree and nature of the specific immunodeficiency . Opportunistic fungal infections are typically associated with cellular rather than (isolated) humoral immuno-deficiencies. Generally, host factors, rather than environmental exposure, are the critical factor in the development of opportunistic mold infection in immunocompromised individuals because exposure to potential fungal opportunistic pathogens (eg, ASP species) is ubiquitous in normal outdoor and indoor environments. Accepted histological and microbiologic methods should be used to make the diagnosis of fungal infection . (328)
TOXIC EFFECTS OF MOLD EXPOSURE ~ TOXICITY CAUSED BY INHALATION
The term mold toxicity as used here refers to the direct injurious effects of mold-produced molecules, so-called mycotoxins, on cellular function.
Only certain mold species produce specific mycotoxins under specific circumstances. Importantly, the mere presence of such a mold should not be taken as evidence that the mold was producing any mycotoxin. For a toxic effect to occur in a subject, (1) the toxin must be present, (2) there must be a route of exposure, and (3) the subject must receive a sufficient dose to have a toxic effect . In the nonoccupational setting the potential route of exposure is through inhalation. Mycotoxins are not volatile and, if found in the respirable air, are associated with mold spores or particulates. They are not cumulative toxins, having half-lives ranging from hours to days depending on the specific mycotoxin . Calculations for both acute and subacute exposures on the basis of the maximum amount of mycotoxin found per mold spore for various mycotoxins and the levels at which adverse health effects are observed make it highly improbable that home or office mycotoxin exposures would lead to a toxic adverse health effects .
Thus, we agree with the American College of Occupational and Environmental Medicine evidence-based statement and the Institute of Medicine draft, which conclude that the evidence does not support the contention that mycotoxin-mediated disease (mycotoxi-cosis) occurs through inhalation in nonoccupational settings . Furthermore, the contention that the presence of mycotoxins would give rise to a whole panoply of nonspecific complaints is not consistent with what is known to occur; when a toxic dose is achieved (eg, through ingestion of spoiled foods), there is a specific pattern of illness seen for specific mycotoxins.
The occurrence of mold-related toxicity (mycotoxicosis ) from exposure to inhaled mycotoxins in nonoccupational settings is not supported by the current data, and its occurrence is improbable. (329)
IMMUNE DYSFUNCTION
The question has been raised as to whether mold or mycotoxin exposure can induce disorders of immune regulation. At this time, there is no credible evidence to suggest that the environmental exposure to molds or their products leads to a state of clinically significant altered immunity expressed as either immunodeficiency or auto-immunity . The published literature in this regard is of particularly poor quality and should not be relied on as scientifically valid. Individuals who have had intense occupational mold exposures do not manifest opportunistic infections or other findings of immunodeficiency, and thus even the most intense form of airborne mold exposure is not a recognized cause of secondary immunodeficiency in human subjects . Some mycotoxins are immunosuppressive and used for this purpose clinically (eg, cyclosporine ). However, the doses involved are not relevant to what might have been found in the environment.
Exposure to molds and their products does not induce a state of immune dysregulation (eg, immunodeficiency or autoimmunity ). (330)
LABORATORY ASSESSMENT
Patient Assessment
Measurement of IgG antibodies to mold proteins . Assessment of IgG antibodies to mold proteins can be performed through immunoprecipitation-double diffusion or solid-phase immunoassays. Such testing has demonstrated value in assessment of individuals with suspected HP or allergic bronchopulmonary mycosis . Such testing (immunoprecipitation or solid-phase IgG testing) is appropriate to perform only in the setting of a clinical picture, including history, physical examination, imaging studies, and other laboratory assessments, suggesting HP or allergic bronchopulmonary mycosis as part of the differential diagnosis . Use of these tests as screening procedures for these diseases in the absence of an appropriate clinical picture is discouraged.
Immunoprecipitation testing remains the standard approach because the presence of precipitating antibodies is strong supportive evidence in the appropriate clinical setting. However, as many as half of highly exposed individuals might have precipitating antibodies in the absence of any clinical disease .
Testing for IgG antibodies to mold proteins cannot be used as a surrogate to assess either the level or timing of specific mold exposures. This is not surprising given the widespread occurrence of molds in the environment . (330-331)
Measurement of molds and mold product exposure in the patient's environment
Measurement of airborne fungal spores in the subject's environment by using culture methods, nonculture methods, or both is commonly used. Air testing provides the most relevant measure of exposure and is usually reported as colony-forming units or spores per cubic meter of air. However, this testing suffers from the drawback that it is a snapshot that does not integrate exposure over time and provides data only about the location of sampling. Indoor testing must be compared with outdoor testing and preferably with more than one outdoor sample. Currently there are no standards as to what constitutes acceptable levels of outdoor or indoor airborne fungal spores.
...Total fungi spores that are greater in concentration in indoor than outdoor air might be potential evidence of increased fungal presence indoors. However, in normal indoor environments xerophillic fungi, such as ASP and PEN species, might be found indoors at levels above those measured outdoors on a given day. Even when the fungal levels are greater indoors than those outdoors, health risks would be limited in most cases, except to the subject specifically allergic to the mold in question. Absolute fungal spore levels indoors can be put into context when one realizes that outdoor levels can reach tens of thousands of fungal spores per cubic meter and hundreds of thousands per cubic meter or higher around rotting vegetation compost or in agricultural settings, such as in grain elevators . (331)
Measurement of fungal products in the patient's environment
Mycotoxins. Specific molds can produce, under some conditions, a variety of mycotoxins or none at all. Thus measurements of spores cannot be used as surrogates of mycotoxin exposure . Mycotoxins can be measured directly. A variety of methodologies based on mass spectroscopy have been applied to bulk samples with heavy fungal growth to identify the presence of mycotoxins; however, potential levels of mycotoxin in non-agricultural air samples are too low to be measured practically with this technology. The occurrence of mycotoxins in bulk sampling does not provide evidence of exposure because mycotoxins themselves are nonvolatile. Thus exposure requires inhalation of mycotoxin-containing spores or fungal fragments in the respirable air. For example, satratoxin H can be found in a sample of material with heavy Stachybotrys chartarum growth, but Stachybotrys species are not easily aerosolized. (331-332)
C. The ACOEM Evidence-Based Statement (2003)
AAAAI (2006) is consistent with the 2003 Evidence-Based Statement of the American College of Occupational and Environmental Medicine (ACOEM) entitled "Adverse Human Health Effects Associated with Molds in the Indoor Environment. The ACOEM concluded inter alia :
Molds and other fungi may adversely affect human health through three processes:
1) allergy; 2) infection; and 3) toxicity. (470)
[Allergy]
One can estimate that about 10% of the population has allergic antibodies to fungal antigens. Only half of these, or 5%, would be expected to show clinical illness. Furthermore, outdoor molds are generally more abundant and important in airway allergic disease than indoor molds, leaving the latter with an important but minor overall role in allergic airway disease. Allergic responses are most commonly experienced as allergic asthma or allergic rhinitis (‘hay fever ’). (470)
[ABPA and AFS (allergic fungal sinusitis ) ] are unusual variants of allergic (IgE-mediated) reactions in which fungi actually grow within the patient's airway. (470) [AFS] presents in subjects who have underlying allergic disease and in whom, because of poor drainage, a fungus colonizes the sinus cavity. (472) ABPA and AFS are uncommon disorders whereas exposure is ubiquitous to the fungal organisms involved. There is no evidence to link specific exposures to fungi in home, school, or office settings to the establishment of fungal colonization that leads to APBA or AFS. (472)
Although it is not relevant to indoor mold exposure, it should be mentioned that there is a belief among some health practitioners and members of the public regarding a vague relationship between mold colonization, molds in foods, and a ‘generalized mold hypersensitivity state.’...The proposed hypersensitivity is determined by the presence of any of a host of non-specific symptoms plus an elevated (or even normal) level of IgG to any of a host of molds. The claim of mold colonization is generally not supported with any evidence, eg, cultures or biopsies, to demonstrate the actual presence of fungi in or on the subject. Instead, proponents often claim colonization or infection based on the presence of a wide variety of nonspecific symptoms and antibodies detected in serological tests that represent no more than past exposure to normal environmental fungi. The existence of this disorder is not supported by reliable scientific data. (472)
[Infection]
Exposure to molds indoors is generally not a specific risk factor in the etiology of mycoses except under specific circumstances as discussed below for individual types of infection. (472) [F]ungal infections in which there is deep tissue invasion are primarily restricted to severely immunocompromised subjects (472) Only individuals with the most severe forms of immunocompromise need be concerned about the potential for opportunistic fungal infections. These individuals should be advised to avoid recognizable fungal reservoirs, including but not limited to indoor environments where there is uncontrolled mold growth. (473)
[Toxicity]
Mycotoxins are ‘secondary metabolites’ of fungi, which is to say mycotoxins are not required for the growth and survival of the fungal species (‘toxigenic species’) that are capable of producing them. The amount (if any) and type of mycotoxin produced is dependent on a complex and poorly understood interaction of factors [I]t does not necessarily follow from the mere presence of a toxigenic species that mycotoxins are also present. (473)
If mycotoxins are to have human health effects, there must be an actual presence of mycotoxins, a pathway of exposure from source to susceptible person, and absorption of a toxic dose over a sufficiently short period of time. (473)
Some molds that propagate indoors may under some conditions produce mycotoxins that can adversely affect living cells and organisms by a variety of mechanisms... Molds growing indoors are believed by some to cause building-related symptoms. Despite a voluminous literature o n the subject, the causal association remains weak and unproven, particularly with respect to causation by mycotoxins. One mold in particular, Stachybotrys chartarum, is blamed for a diverse array of maladies when it is found indoors. Despite its well-known ability to produce mycotoxins under appropriate growth conditions, years of intensive study have failed to establish exposure to S. chartarum in home, school, or office environments as a cause of adverse human health effects. Levels of exposure in the indoor environment, dose-response data in animals, and dose-rate considerations suggest that delivery by the inhalation route of a toxic dose of mycotoxins in the indoor environment is highly unlikely at best, even for the hypothetically most vulnerable subpopulations. (475-476)
Current scientific evidence does not support the proposition that human health has been adversely affected by inhaled mycotoxins in home, school, or office environments. (476)
D. Dr. Michael Phillips' Testimony Concerning AAAAI (2006)
Dr. Michael Phillips, Defendant's expert, testified that the AAAAI Position Statement has never been retracted (MP 551), that it is still followed by the vast majority of AAAAI's members (MP 552), and that it is still accepted by the general medical community as correct. (MP 50) Concerning specific principles affirmed by AAAAI (2006), Dr. Phillips testified:
Mold is ubiquitous. The body's physical barriers and immune system are human defense mechanisms to mold. Consequently, host factors, and not environmental exposure, are the main determinant of opportunistic mold infection. (MP 556-557)
There is no medically accepted threshold for mold/mycotoxin exposure that is considered to be associated with specific human disease. The levels of exposure possible under normal conditions are below the threshold that would cause clinically significant disease. (MP 583, 600, 616)
Direct infection occurs almost exclusively in patients with impaired immune systems; in such cases, mold grows despite attempts by the immune system to control it. (MP 556-557, 583)
Mold and its byproducts do not induce immune dysregulation. (MP 567, 665)
Inhaled mycotoxins in the home environment do not adversely affect human health. (MP 582) Nonoccupational inhalation of mycotoxins does not cause mycotoxicosis. The half-life of mycotoxins is very short, hence their effects are short-lived and very acute. Mycotoxins do not live in the human body because the body breaks down toxins. (MP 563-565)
Mold causes acute infection. It does not live in the body producing mycotoxins over long periods of time. That is biologically impossible. (MP 59)
E. Dr. Irene Grant's Acknowledgment That The General Principles Reflected In AAAAI (2006) Represented The General Consensus Until 2012
While criticizing AAAAI's 2006 Position Statement in various respects, Dr. Grant nevertheless tacitly acknowledged both on her internet website and in her Frye hearing testimony that it reflected the general consensus until about 2012.
Her internet website, in 2010, contained the following statements:
"Mold-related illness is an area of medical science that is only recently beginning to be spotlighted."
"Diagnosing mold infection is difficult and often inductive even with the finest medical procedures and laboratories."
"Although research in animals on infectious complications and toxic effects of the dangerous molds is substantial, research defining the medical impact on humans is scarce due to ethical constraints."
"Molds are generally accepted to cause allergies or deep infections in those with weakened immune systems."
"Whether the molds continue to produce the same toxins inside the human body as they do in their natural environment is an area for further study."
(IG 221-224; Deft. Ex. "B")
At the Frye hearing Dr. Grant testified inter alia :
In 2011, the science of the effects of mold on human health was still unfolding. (IG 80)
Her diagnosis of JL in 2011 was not generally accepted as a means of diagnosis in 2011. (IG 68)
It is only since 2012 that there exists literature that supports her theory of causation. (IG 227, 250)
Even today it is not known what level of mycotoxins pose a risk to human health. (IG 413, 420-421)
As of 2017, the medical community did not accept that mold produces mycotoxins in the human body. (IG 244-245)
While Dr. Grant took issue with the AAAAI (2006) conclusion that the occurrence of mold-related toxicity from exposure to inhaled mycotoxins in nonoccupational settings is improbable, she proffered no literature reflecting a consensus of infectious disease experts to the contrary. (IG 465-466)
F. Review of Pertinent Scientific Literature
Abiding by the Court of Appeals' decision in Cornell and taking into account Dr. Grant's admissions as set forth above, the Court reviews scientific literature from 2012 onwards (plus selected earlier articles on which Plaintiff has placed significant reliance) in order to determine whether Dr. Grant's theory of causation and method of diagnosis are generally accepted by the scientific community (consisting of allergists, immunologists, occupational and environmental scientists, and infectious disease specialists). More specifically, the question here is whether scientific/medical developments have altered in respects material to this case the general consensus on the medical effects of mold exposure reflected in AAAAI (2006).
Tab 8 Bongomin, et al., Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis (2017)
This study evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). (1) Aspergillus fumigatus is a ubiquitous, opportunistic airborne mold capable of causing bronchopulmonary disease in susceptible individuals. (1) In the normal host, synergistic and highly coordinated interaction between the innate and adaptive arms of the immune system ensures that inhaled ASP conidia do not cause disease. (2) Inherited (genetic) and acquired aberrations in these complex networks of interactions in antifungal immunity, coupled with local pulmonary epithelial compromise predispose to the development of a variety of pulmonary syndromes in response to ASP. (2) [This is fully consistent with AAAAI (2006) ]
The authors state that "[i]n this study, we established that significant CD3, CD4, CD8, CD19, and CD56 lymphopenia occurs in patients with CPA" (9), and that the study is "the first of its kind to provide direct evidence of considerable defects in both the innate and adaptive arm of the immune system in the majority of patients with CPA." (11) However, they further note that "absolute T- and B-lymphocyte counts can be influenced by many factors such as infections and medications compared to the relatively stable percentage total lymphocyte counts. CPA is a chronic infection; therefore, it cannot be established if CPA is the cause or the consequence of the immunological alterations ." (Bongomin 11)
Dr. Grant asserts that JL's low CD4 count predisposed her to developing an opportunistic fungal infection. (283-288) However, CD4 testing is not sensitive or specific to mold (Bongomin 11; MP 572-573, 619); and JL's low CD4 count was ascertained for the first time in March 2013, long after her alleged mold exposure, and after Dr. Grant had placed her on a regime of anti-fungal medication which is itself immunosuppressive. (March 2017 Expert Report, 5; MP 571). Dr. Grant acknowledged that (as per Bongomin, p. 11) the question whether CPA causes immunosuppression or vice-versa is a subject of ongoing research. (IG 287) Accordingly, it does not alter the general consensus that, contrary to Dr. Grant's opinion, exposure to molds and their byproducts does not induce a state of immune dysregulation. (AAAAI [2006] 330)
Tab 11 Brewer, et al., Chronic Illness Associated with Mold and Mycotoxins (2014)
This article is a survey of literature, not the product of a study. (66) The authors hypothesized that patients who develop chronic illness after prior exposure to water-damaged buildings harbor mold internally which continues to release and/or produce mycotoxins which contribute to ongoing chronic illness. (66) Relative to Dr. Grant's theory of causation, the authors conclude: "Humans and animals with IA [Invasive Aspergillosis ] have gliotoxin and aflatoxins in their sera and tissues. These observations suggest that ASP species produce mycotoxins during IA." (74) "Prior exposure to toxic mold and mycotoxins may represent an important feature of chronically ill patients such as CFS [chronic fatigue syndrome ] as well as those with CRS [chronic rhinosinusitis ]. An internal reservoir of toxin producing mold (e.g., sinuses) that persists in biofilms could produce and release mycotoxins. This model of fungal persistence may help explain these chronic illnesses and represent a potential new understanding of mechanisms of disease that can be treated and/or lessened." (74)
Preliminarily, Dr. Grant did not diagnose JL with IA, but rather with chronic Aspergillosis (IG 440, 483), and hence the author's suggestion that ASP may produce mycotoxins during IA is irrelevant here. Moreover, the authors' conclusions are obviously provisional -- suggestions, possibilities, potential new understandings -- and do not even remotely reflect a general acceptance within the medical community of the authors' theory -- key to Dr. Grant's theory of causation -- that patients who develop chronic illness after prior exposure to water-damaged buildings harbor mold internally which continues to release and/or produce mycotoxins which contribute to ongoing chronic illness.
Tab 12 Bugli, et al., Increased production of gliotoxin is related to the formation of biofilm by Aspergillus fumigatus: an immunological approach (2014)
Plaintiff did not specifically rely on this paper at the Frye hearing. The authors developed an antibody against gliotoxin (GT), produced by A. fumigatus, and showed that it "holds promise" for the diagnosis of A. fumigatus infection in the human host. (379) They wrote:
"In this study, we generated an anti-GT mouse polyclonal antibody (pAb) to develop an immunofluorescent assay that allowed to elucidate the relationship between A. fumigatus biofilm growth phenotype and GT production. This assay proved to detect GT not only on hyphae cultured onto the cell line A549, but also, directly, on hyphae into respiratory tract specimens or lung tissues from patients with invasive aspergillosis (IA). As the presence of fungal hyphae in clinical specimens strongly indicates the in vivo A. fumigatus growth as a biofilm, anti-GT antibodies were envisaged as a specific and sensitive diagnostic tool for detecting A. fumigatus biofilm-associated clinical infections." (380)
The authors further noted: "[T]here is evidence that GT is produced in the infected organs of patients with aspergillosis at a significant level [cit.], as GT was detected in the lungs and sera of mice with experimental IA and in the sera of patients with cancer with IA [cit.]. Interestingly, GT concentrations in serum were substantially lower than the lung tissue concentrations [cit.], according to the evidences that GT as well as bmGT are synthesized by A. fumigatus only in the hyphal stage [cit.]...." (386)
Once again, Dr. Grant did not diagnose JL with IA, but with chronic aspergillosis (440, 483). Moreover, Dr. Grant's diagnosis was predicated, in part, on the presence of ochratoxin in JL's sinuses and urine; no gliotoxins were detected in JL's body. (IG 67; Br. Par. 30) In view of the foregoing, it is unclear how this study has any bearing on the issues before the Court.
Tab 14 Carey, et al., Satratoxin-G from the Black Mold Stachy chartarum Induces Rhinitis and Apoptosis of Olfactory Sensory Neurons in the Nasal Airways of Rhesus Monkeys (2012)
"Satratoxin-G (SG) is a trichothecene mycotoxin of Stachybotrys chartarum, the black mold suggested to contribute etiologically to illnesses associated with water damaged buildings To further assess the potential human risk of nasal airway injury and neurotoxicity, we developed a model of SG exposure in monkeys, whose nasal airways more closely resemble those of humans... This model provides a new insight into the potential risk of nasal airway injury and neurotoxicity cause by exposure to water-damaged buildings." (887)
The authors acknowledge that "[o]ne of the principal arguments against the hypothesis that S. chartarum causes adverse health effects in people is that the concentrations of Stachy reported to cause toxicity in animal studies may not be achieved in water-damaged indoor air environments." (895) While they attempt to address this argument, the authors acknowledge that: (1) their study represents only an "intermediate step in the extrapolation of data from rodent models for human risk assessment"; (2) their model "may address critical gaps in the association between exposure to damp buildings and reported neurologic symptoms "; (3) "appropriate translational research is urgently needed to elucidate the potential health risks to people "; and (4) that their data should "serve as the basis for future investigations using this model to determine whether intranasal SG exposure is capable of causing injury to the CNS [central nervous system], to determine the persistence of SG-induced olfactory system injury, and ultimately, to determine whether SG-induced nasal and neuronal injury are temporally associated with neurobehavioral and neurocognitive injury." (896-897)
Once again, the authors' conclusions are obviously provisional, they recognize the analytical gap between the results of their animal study and the causation of mold-related disease in human subjects, and they merely raise, and do not answer, the question whether inhalation of mycotoxins and/or trichothecenes in indoor environments bears a causal relation to the development of clinical human disease.
Tab 15 Carpagnano, et al., Aspergillus spp. Colonization in exhaled breath condensate of lung cancer patients (2014)
"This was a preliminary study that aimed to analyse the incidence and nature of fungal colonization in lung cancer patients from Region Puglia of Italy." (3) The authors "couldn't verify whether fungal colonization is the cause or consequence of lung cancer", and "were unable to find any correlation between fungi positivity and sex, age, histotype, stage, smoking habit of subjects studied that would help us in the definition of the pathogenic role of fungi identified in the cancer patients." (4)
Mold is ubiquitous, and many people are colonized by aspergillus. (MP 16) This study does nothing to elucidate the pathogenic role of ASP in the human body.
Tab 16 CDC Case Definition: Trichothecene Mycotoxin Poisoning (2013)
Citing a 1997 textbook of military medicine discussing the intentional dissemination of trichothecenes for chemical and biological warfare, the CDC states that inhalation of trichothecenes can result in the development of "systemic symptoms" and "might include weakness, ataxia, hypotension, coagulopathy, and death." However, toxicity is dose and time related. Unless studies deal with levels of exposure which are possible under normal conditions, any proposed causal relationship to clinical human disease is merely conjectural. (MP 547-548, 616-618) Hence, the CDC Case Definition does not alter the AAAAI (2006) consensus that the occurrence of mold-related toxicity from exposure to inhaled mycotoxins in nonoccupational settings is improbable.
The CDC also states that "[s]elected trichothecene mycotoxins can be detected in human urine to assess for exposure." Since the human body does not produce trichothecenes, their existence in urine is evidence of exposure, but the CDC does not state that this is diagnostic of human disease. (MP 627-628) In 2015, the CDC reported: "Mycotoxins are metabolites of some fungi that can cause illness in humans and animals, primarily after ingestion of contaminated foods. Low levels of mycotoxins are found in many foods; therefore, mycotoxins are found in the urine of healthy persons. Mycotoxin levels that predict disease have not been established. Urine mycotoxin tests are not approved by FDA for accuracy or for clinical use." Kawamoto et al., Use of Unvalidated Urine Mycotoxin Tests for the Clinical Diagnosis of Illness (2015).
Tab 17 Chotirmall, et al., Immunoevasive Aspergillus Virulence Factors (2014)
This is a review article focusing on "the interaction between Aspergillus pathogenic mechanisms, host immune responses and the immunoevasive strategies employed by the organism during disease states such as that observed in cystic fibrosis." (363) The authors note:
"Aspergillus is a ubiquitous fungal species causing disease in ‘at risk’ individuals such as those with structural lung disease or defective immune states." (363)
"Conidial-host interaction particularly in the context of pulmonary disease remains poorly understood . Spore inhalation incites a series of cascading events whose course is determined by the underlying immune state of the affected individual." (363)
"Inhaled daily, Aspergillus spore exposure in the immunocompromised host initially triggers innate immune defenses in an attempt to combat and remove the offending organism. Such mechanisms include the physical and mechanical barriers of the respiratory tract including mucociliary clearance and activation of phagocytic cells such as neutrophils and macrophages." (364)
"Progression from innocuous fungal inhalation to potentially lethal invasive pulmonary disease is intrinsically linked with host immune status. Failure to successfully clear inhaled conidia, a concern in immunocompromised states may result in angioinvasion and systemic aspergillosis with high mortality rates. Interestingly, only a proportion of patients within these ‘at risk populations’ actually develop IA despite daily fungal exposure." (365)
"A. fumigatus-derived toxins represent an important and further mode of conferring immune evasion. Considered secondary metabolites, fungal toxins are putative virulence factors critical in mediating Aspergillus-associated disease. [T]he most important is gliotoxin... produced by almost all clinical strains of A. fumigatus. It is readily detected in vivo animal models and importantly in patients with IA [invasive aspergillosis ]." (366)
"The role of fungi in the context of cystic fibrosis (CF) is being increasingly recognized and CF patients remain at increased risk of fungal acquisition, colonization and infection for reasons similar to that for bacterial colonization. Defective mucociliary clearance coupled with regional immune dysfunction promotes fungal establishment and limits its clearance" (367)
The authors conclude:
"It is evident that Aspergillus pathogenicity depends on both host- and fungal-derived factors. The underlying immune state of the host coupled to the virulence capability of the infecting strain determines the speed and severity of ensuing colonization, infection and systemic disease." (368)
"Improving our understanding of the relationship between host and fungus particularly in the context of the immune response and evasive strategies will allow an exploration of emerging pathways and investigation of potential novel therapeutic agents." (368)
This article is fully consistent with the AAAAI (2006) consensus that it is "at risk" individuals with immune deficiencies and/or structural lung disease who are vulnerable to serious illness from the inhalation of mold and mold byproducts because their natural defense mechanisms to the ubiquitous ASP are compromised. (MP 633) There is no evidence that JL was immunodeficient or that she had structural lung disease at the time of the alleged mold exposure in 2011. Insofar as gliotoxins are "putative" virulence factors critical in mediating ASP-associated disease, the evidence shows that they are found in patients with IA, but Dr. Grant did not diagnose JL with IA (IG 440, 483), and gliotoxins were not detected in JL's body. (IG 67; Br. Par. 30) Finally, the authors acknowledge that "conidial-host interaction particularly in the context of pulmonary disease remains poorly understood ," and that an improved understanding would "allow an exploration of emerging pathways and investigation of potential novel therapeutic agents."
Hence, despite Plaintiff's heavy reliance on this article (B. Par. 78-81), it is not reflective of a general acceptance of Dr. Grant's theory of causation.
Tab 18 Cole, et al., Improvement of fungal disease identification and management: combined health systems and public health approaches (2017)
Plaintiff did not specifically rely on this paper at the Frye hearing. It is essentially a survey of issues in public health management of fungal-related illness which is not of significance to the matter before the Court.
Tab 22 Denning, et al., Chronic pulmonary aspergillosis : rationale and clinical guidelines for diagnosis and management (2016)
This paper concerns the requirements for a clinical diagnosis of chronic pulmonary aspergillosis (CPA). The authors state:
"CPA is an uncommon and problematic pulmonary disease," which is "found in non-immunocompromised patients with prior or current lung disease." (45)
"Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months." (45; see 51)
Imaging: "Chest radiographs remain the first imaging modality for the suspicion and diagnosis of CPA (Table 7). CT of thorax offers much additional value, as it provides better definition and location of imaging abnormalities as well as their distribution and extent." (54)
Imaging findings: "The imaging features of CPA result from a combination of the findings related to underlying lung disorders and changes secondary to Asp infection itself, reflecting the chronic inflammatory and immune response to Asp spp. Changes secondary to the Asp infection itself range from the typical appearance of a fungus ball within a lung cavity...to complex pleuroparenchymal features that are related to a progressive destructive cavitary disease. (55)
Diagnosis: "If a fungal ball is observed, then confirmation that Aspergillus is responsible requires only an Aspergillus IgG or precipitens test to be positive, which it will be in >90% of cases" (51) Per Table 6, where there is evidence of "cavitary or nodular pulmonary infiltrate in non-immunocompromised patients," then the presence of Aspergillus antibodies is diagnostic of CPA. (53-54)
Preliminarily, it does not appear that JL was diagnosed with CPA; Dr. Grant's diagnosis of chronic Aspergillosis appears to be predicated on alleged infection of the sinuses, not the lungs. Dr. Grant evidently proffers this article, and others by David Denning (see Tabs 37, 43, 45, 46) as proof of the diagnostic usefulness of a positive IgG antibody titer. However, the article plainly states that at immunological response to Asp spp. is meaningful only in the context of multiple characteristics, including one or more cavities with or without a fungal ball present or nodules on thoracic imaging, the exclusion of alternative diagnoses, and the IgG titer itself, "all present for at least 3 months." This is fully consistent with the AAAAI (2006) position regarding "patient assessment" (330-331). By itself, an elevated IgG titer is not diagnostic of specific disease or indicative of the details of exposure. (MP 575-576)
Tab 23 Dennis, et al., Nasal Fungal Pathology and Tricocethines Associated with Water-Damaged School and Home (2016)
Plaintiff relies heavily on this article (B. Par. 90-99), but it is only a case report. Based on observations made in a single case, the authors state that "it appears that fungi and bacteria along with their secondary metabolites are important factors in illness of occupants in water-damaged homes, schools and office buildings." (4) "[C]ase reports are not generally accepted in the scientific community on questions of causation." Heckstall v. Pincus , 19 AD3d 203, 205 (1st Dept. 2005). See, Pauling v. Orentreich Med. Group , 14 AD3d 357, 358 (1st Dept. 2005). (MP 636)
Tab 24 Doi, et al., Mechanisms of Mycotoxin-Induced Neurotoxicity through Oxidative Stress-Associated Pathways (2011)
This is a review of literature concerning the mechanisms of neurotoxicity induced in rodents by mycotoxins including macrocyclic tricocethines. (5213, 5224)
The authors observe: "Chronic indoor exposures to S[tachybotrys] chartarum and its components have been postulated to etiologically contribute to damp building-related illnesses (DBRI) such as debilitating respiratory and nonrespiratory symptoms involving immune and neurological impairment. Experimental rodent studies revealed that, while this fungus is not infectious, airway exposure to spores of S. chartarum and its components have the potential to evoke toxicity, inflammation and allergic sensitization in the upper and lower respiratory tracts." (5216)
The authors cite Pestka, et al., Stachybotrys chartarum, Trichothecene Mycotoxins, and Damp Building-Related Illness: New Insights into a Public Health Enigma (2008), which states that "there is currently inadequate evidence to establish a definite linkage between [Stachybotrys and its byproducts] and DBRI" (18), and explains the limited bearing of the extant rodent studies on the determination of the cause of human illness in the context of DBRI:
"Animal studies of Stachybotrys have employed many different experimental designs, making results difficult to compare because of numerous variables including spore viability, mycotoxin content, inclusion of submicron-sized mycelial fragments, and the presence of fungal proteins. Well-characterized, standardized preparations of fungal spores, and mycelial fragments with properties representative of those found in indoor air are needed to elucidate mechanisms that might be contributory to adverse health effects. Development of experimental conditions that mimic chronic exposure to low doses and coexposure with other environmental factors will allow animal studies to more accurately reflect human indoor exposure. Ultimately, resolving the public health enigma of whether and how Stachybotrys inhalation evokes adverse health effects that contribute to DBRI will require state-of-the-art sampling/analytical methods to assess doses and timing of exposure to the fungus and its bioactive constituents as well as exploiting the use of relevant biomarkers." (21)
Hence, despite Plaintiff's heavy reliance on this article (B. Par. 100-110), it is not by itself reflective of a general acceptance of Dr. Grant's theory of causation.
Tab 26 Fromme, et al., Overall internal exposure to mycotoxins and their occurrence in occupational and residential settings -- An overview (2015)
"[T]his review aims in summarizing literature data on potentially inhalable mycotoxins occurring in dusts or air in residences and in working environments. Secondly, it gives an overview of the overall internal body burden of mycotoxins in humans in an attempt to characterize total human exposure. These data are also discussed in relation to the current toxicologically based values used for risk assessment." (1)
The authors observe: "Overall, it is very difficult to conduct a risk assessment of airborne mycotoxins due to a lack of reliable data on inhalative toxicity and respirable concentrations in the air, as well as a lack of standardized methods for sampling and examination. This is further aggravated by the individual sensitivity of different people toward (microbial) volatile organic compounds and air contaminants and the multifactural nature of human health disorders in the context of dampness, mold or respiratory dust exposure." (4)
While acknowledging that information concerning inhalative exposure to mycotoxins in water-damaged residences is limited, the authors state that "in most of the samples, the concentrations [of mycotoxins] in residences are near or below the LOQ" [limit of quantification]. (4)
Citing Bui-Klimke, et al., Ochratoxin a and human health risk: a review of the evidence (2015), the authors state that "all epidemiologic studies showed no statistically significant evidence for human health risks associated with OTA exposure or have methodological limitations ." (11)
In sum, although Plaintiff relies heavily on this article (B. Par. 51-62), nothing in this review of literature supports Dr. Grant's theory of causation.
Tab 30 Inamdar, et al., Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration (2013)
The authors themselves describe the significance of their study: "Poor air quality from fungal growth in water-damaged, moldy buildings/residences is correlated with a negative impact on human health. The volatile organic compound 1-octen-3-ol is commonly emitted by molds and is responsible for much of the distinctive moldy odor associated with fungal colonization. Using a Drosophila model [i.e., fruit flies], we demonstrate via genetic, bio-chemical, and immunological studies that 1-octen-3-ol causes dopomine neuron degeneration through disruption of dopamine handling. These data demonstrate that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism. Moreover, it provides possible insights into reported movement disorders associated with human exposure to fungi and their volatile organic compounds." (1)
At most, then, this study demonstrates a correlation or possible link between inhalation of mold indoor environments and neurodegeneration. Per Cornell , this is patently insufficient to establish general causation.
Tab 35 Karunasena, et al., Building-Associated Neurological Damage Modeled in Human Cells: A Mechanism of Neurotoxic Effects by Exposure to Mycotoxins in the Indoor Environment (2010)
This is an in vitro study, the stated purpose of which was "to identify the mechanisms, in human neurological system cells, that induce cell damage from exposure to the trichothecene mycotoxin satrotoxin H (SH)." (379) "[T]he objective of these experiments was to evaluate the effects exposure to SH would have on cellular homeostasis and to determine whether a model of the [blood brain barrier] could be compromised and neural cell damage could be induced by exposure to macrocyclic trichothecenes at low concentrations that may be present in buildings with poor [indoor environmental quality] as determined through ELISA quantification of trichothecene levels." (379)
The authors state that their results "suggest that low to moderate levels of SH are able to induce inflammatory and apoptotic pathways that amplify cellular damage by the continuous activation of these biological pathways." (385) They further state that "[t]his study suggests that individuals exposed to SH and microbial organisms resulting in a chronic immune response (inflammation and oxidative stress ) could have increased sensitivity to these agents, leading to neural damage" (385) They conclude that they have shown "that neurological system cell damage is a potential public health threat " that is "not fully understood ." (385)
Consistent with her admissions as set forth above, Dr. Grant acknowledged that this 2010 study established not causation, but only an association between neurological damage and exposure to mycotoxins in indoor environments. (IG 391-394)
Tab 37 Kosmidis and Denning, The Clinical Spectrum of Pulmonary Aspergillosis (2015)
See Tab 22.
Tab 39 Kurosaki, et al., Clinical features of pulmonary aspergillosis associated with interstitial pneumonia (2014)
Plaintiff did not specifically rely on this paper at the Frye hearing.
Tab 41 Limonciel, et al., A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity (2014)
Plaintiff did not specifically rely on this paper at the Frye hearing. Based on their review of the literature, the authors concluded that "there is compelling evidence that OTA's inhibition of Nrf2 is the mechanism for both its nephrotoxicity and carcinogenicity." (376) It is not clear how, if at all, nephrotoxicity or carcinogenicity is relevant to this case, but in any event the authors' concern is exposure to OTA via ingestion of foodstuffs and not through inhalation. (371-372)
Tab 43 Muldoon, Denning et al., Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis (2016)
See Tab 22.
Tab 45 Page, Denning et al., Antibody testing in aspergillosis -- quo vadis? (2015)
In this review article, the authors begin by observing: "Humans are constantly exposed to airborne Aspergillus spores. Most develop Aspergillus-specific antibodies by adulthood. Persons with chronic lung disease or Aspergillus airway colonization often have raised levels of Aspergillus-specific immunoglobulin G (IgG). It is not known whether this signifies an increased risk of future aspergillosis." (417) Since "[t]he antibody response to Aspergillus and thus the role of antibody measurement in diagnosis and management varies greatly from one syndrome to another" (418), the authors consider the role of antibody testing in diagnosing various forms of aspergillosis.
"The vast majority of patients with aspergillosis have one or more underlying disorders and the presentation of aspergillosis varies in line with the underlying disorder." (418) The syndrome most closely approximating Dr. Grant's diagnosis of JL the authors describe as a form of "sub-acute invasive pulmonary aspergillosis" called "chronic invasive fungal rhinosinusitis." The authors write: "[S]ub-acute invasive pulmonary aspergillosis ] is normally seen in patients with mild immunosuppression due to diabetes, steroid use, alcoholism, COPD, tuberculosis or AIDS. A similar condition occurs in the sinuses, where it is termed chronic invasive fungal rhinosinusitis. Diagnosis of sub-acute invasive aspergillosis is based on a combination of symptoms, radiological changes and laboratory tests, including antibody and antigen tests or culture ." (419)
Once again, then, Dr. Denning observes that the IgG titer is meaningful only in the context of multiple characteristics -- here, "a combination of symptoms, radiological changes and laboratory tests, including antibody and antigen tests or culture." This is fully consistent with the AAAAI (2006) position regarding "patient assessment" (330-331). By itself, an elevated IgG titer is not diagnostic of specific disease or indicative of the details of exposure. (MP 575-576)
Tab 46 Patterson, Denning, et al., Practice Guidelines for the Diagnosis and Management of Aspergillosis : 2016 Update by the Infectious Diseases Society of America (2016)
See Tab 22.
Tab 50 Polizzi, et al., Identification of volatile markers for indoor fungal growth and chemotaxonomic classification of Aspergillus species (2012)
This study involved the use of microbial volatile organic compounds (MVOCs) as possible indicators of indoor fungal growth. The authors identified species specific patterns of MVOCs for strains of Aspergillus other than Aspergillus fumigatus, the mold at issue in this case. No VOCs were detected or measured in the Defendants' home, where JL was purportedly exposed.
Tab 55 Rocchi, et al., Evaluation of invasive aspergillosis risk of immunocompromised patients alternatively hospitalized in hematology intensive care unit and at home (2014)
This case study involved the incidence of invasive aspergillosis in highly immunocompromised neutropenic patients. JL was not diagnosed with invasive aspergillosis, nor was she highly immunocompromised in 2010-2011 at the time of her mold exposure.
Tab 57 Rosenblum, et al., Environmental Mold and Mycotoxin Exposures Elicit Specific Cytokine and Chemokine Responses (2015)
The authors sought "to understand changes in cytokine and chemokine levels in response to mold and mycotoxin exposures and to link these levels with respiratory symptoms in humans." (Cytokines and chemokines are "mediators of inflammatory and immune system responses.") They conclude that their "findings demonstrate that chronic mold exposures induced changes in inflammatory and immune system responses to specific mold and mycotoxin challenges. These responses can differentiate mold-exposed patients from unexposed controls." (1-3, 16)
The authors went on to state that "[o]ur results support a link between respiratory illness and human cellular immune and inflammatory responses that have been previously reported." They acknowledge, however, that "[b]ecause similar cytokine and chemokine responses could be caused by other inflammatory or immune responsive agents such as other allergens or bacteria and we don't have industrial hygiene reports from the buildings where unexposed control subjects work, a larger clinical study that better characterizes the environment where control subjects work will be required to fully validate a cellular ex vivo test that can be used to characterize human health effects from exposures to individual molds." (15)
In other words, what the authors demonstrated is that if a person is exposed to a mold, he can be sensitized to it, and will respond differently upon the next exposure. That is a "truism of immunology", and the "basis of vaccination." (MP 644-645) However, the study "does not suggest that the response can be used to diagnose human disease, only previous exposure." (MP 647)
Tab 65 Stopinseki, et al., Fungal cell wall agents and bacterial lipopolysaccharide in organic dust as possible risk factors for pulmonary sarcoidosis (2016)
Plaintiff did not specifically rely on this paper at the Frye hearing.
IV. CONCLUSIONS OF LAW
A. General Causation
Based on the review above of the medical / scientific literature proffered by Plaintiff, the Court concludes that Plaintiff has failed to demonstrate that the general consensus reflected in AAAAI (2006) has changed in any respect material to her case.
Plaintiff claims that JL's inhalation of mycotoxins while residing at Defendants' premises contributed to the breakdown of her barrier defense system, facilitating mold infiltration and infection, as well as her initial cognitive and neurological symptoms, and that the remainder of JL's health impairments, and their development over time, resulted from a chronic Aspergillosis infection and the mold's production of mycotoxins inside her body during its infectious state. (See, B. 1, Par. 47; RB. 1) Dr. Grant's theory of causation is wholly at odds with the general consensus, reflected in AAAAI (2006) as well as in the ACOEM Evidence-Based Statement, that:
(1) Since mold is ubiquitous inside and outside, predisposing host factors in the patient (eg, immunodeficiency disorders ) are the critical factor in the development of opportunistic mold infection. Immunocompetent individuals, even with intense occupational mold exposure, do not manifest opportunistic infection or immunodeficiency.
(2) Mycotoxin-mediated disease does not occur through inhalation in nonoccupational settings.
(3) Exposure to molds and their byproducts does not induce a state of immune dysregulation.
Plaintiff has not shown, and indeed has not seriously attempted to show, that it is generally accepted by allergists, immunologists, occupational and environmental scientists, or infectious disease specialists that (1) inhalation of mold and its byproducts in nonoccupational settings causes mycotoxin-mediated disease; or (2) immunocompetent individuals manifest serious opportunistic mold infection; or (3) exposure to mold and its byproducts induces a state of immune dysregulation. Instead, Plaintiff proffers scientific articles which, whether considered individually or collectively, at best support a putative linkage or correlation -- and not a causal relationship -- between the inhalation of mold/mycotoxins in nonoccupational indoor environments and human disease by showing that these agents can cause certain injurious effects in animals, in vitro or otherwise in conditions insufficiently related to their inhalation by humans in nonoccupational indoor environments.
However, it was precisely this approach that the Court of Appeals rejected as insufficient in Cornell . Here, as in Cornell , Plaintiff's expert "departed from the generally accepted methodology for evaluating epidemiologic evidence when determining whether exposure to an agent causes a harmful effect or disease." Id., 22 NY3d at 783.
Epidemiologists are ultimately interested in whether a causal relationship exists between an agent and a disease. However, the first question an epidemiologist addresses is whether an association exists between exposure to an agent and disease. An association between exposure to an agent and disease exists when they occur together more frequently than one would expect by chance. Although a causal relationship is one possible explanation for an observed association between an exposure and a disease, an association does not necessarily mean that there is a cause-effect relationship [cit.om.].
Thus, studies that show an association between a damp and moldy indoor environment and the medical conditions that Dr. Johanning attributes to Cornell's exposure to mold (bronchial-asthma, rhino-sinusitis, hypersensitivity reactions and irritation reactions of the skin and mucous membranes) do not establish that the relevant scientific community generally accepts that molds cause these adverse health effects. But such studies necessarily furnish ‘some support’ for causation since there can be no causation without an association (although, as explained, there can be an association without causation). For these reasons, the Appellate Division was incorrect when it ruled that the Frye standard was satisfied in this case because Dr. Johanning's opinions as to general causation find ‘some support’ in the record. In sum, then, Cornell has not raised a triable issue of fact with respect to general causation."
Id. , at 783. In the wake of Cornell , the Court of Appeals has reaffirmed that the mere existence of some scientific support in the record is insufficient to establish "general acceptance" under Frye . The proponent's burden is to establish a "consensus in the scientific community." See, People v. Williams, 2020 WL 1516488 at *6 (March 31, 2020) ; Sean R. ex rel Debra R. v. BMW of North America, LLC, 26 NY3d 801, 809 (2016).
Finally, Plaintiff places great weight on Dr. Grant's own clinical research based on the treatment of her patients with anti-fungal medication. As a preliminary matter, "general acceptance" under Frye must be demonstrated "through scientific or legal writings, judicial opinions, or expert opinions other than that of the proffered expert ." Dovberg v. Laubach , 154 AD3d 810, 813 (2d Dept. 2017). In any event, as one Court has observed concerning Dr. Grant personally, "her own research...was not conducted in accordance with generally accepted methodology for making determinations about medical causation." Rosati v. Brigham Park Co-op. Apartments, Sec. No. 2, Inc., 36 Misc 3d 1214(A) at *14 (Sup. Ct, Kings Co. 2012) (Battaglia, J.).
Dr. Grant based her opinions in part on her own clinical research, which she described variously as ‘observational clinical research’, ‘prospective observational type research’, and ‘prospective case study’. In oversimplified terms, Dr. Grant treated individuals identified as having ‘significantly heavy mold exposure’ with anti-fungal therapy, and tracked the results, concluding that ‘removal of the fungi removes the trouble’ [cit.om.]. Although Dr. Grant would disagree, courts have determined that ‘observational studies or case reports are not generally accepted in the scientific community on questions of causation.’ (See Heckstall v. Pincus, 19 AD3d 203, 205 [1st Dept. 2005] ; see also Pauling v. Orentreich Med. Group, 14 AD3d 357, 358 [1st Dept. 2005]."
Id., at *15. Judge Battaglia went on to note that one Second Department case characterized such data as "of a lesser caliber than controlled clinical studies from which results can be reviewed and verified." See, Ratner v. McNeil-PPC, Inc., 91 AD3d 63, 76 (2d Dept. 2011). Regardless, Dr. Grant's observational research can establish no more than a correlation or association, and is insufficient under Cornell to demonstrate general causation in accordance with the dictates of Frye .
Citing Lugo v. New York Health & Hosps. Corp., 89 AD3d at 62, and the underlying First Department opinion in Cornell, 95 AD3d at 58, the Rosati Court went on to hold that "Plaintiff has shown that ‘a reasonable quantum of legitimate support exists in the literature for his experts' views’ on general causation." Id., 36 Misc 3d 1214(A) at *25. In Cornell , however, the Court of Appeals held that to be an improper dilution of the Frye standard, which requires general acceptance in the relevant scientific community. See id. , 22 NY3d at 780-783.
In view of the foregoing, the Court concludes that Plaintiff has not established general causation.
B. Specific Causation
Plaintiff seeks to bring her case within the existing consensus that a variety of human illnesses are caused by intense occupational mold / mycotoxin exposures of the kind experienced in certain agricultural and industrial settings. She claims that her exposure to mold and mycotoxins in her basement apartment was significantly greater than in the usual indoor residential environment, and approximated that occurring in agricultural / industrial environments. The predicate for this claim is that (1) air quality testing conducted after she vacated the apartment in May 2011 revealed a high level of airborne Aspergillus fumigatus spores (ca. 45,000 spores per cubic meter) as well as the existence of airborne Stachybotrys spores, and (2) she regularly exercised on a treadmill in the basement, thereby increasing the rate at which she would have inhaled the airborne spores.
"It is well established that an opinion on causation should set forth a plaintiff's exposure to a toxin, that the toxin is capable of causing the particular illness (general causation) and that plaintiff was exposed to sufficient levels of the toxin to cause the illness (specific causation)... [I]t is not always necessary for a plaintiff to quantify exposure levels precisely or use the dose-response relationship, provided that whatever methods an expert uses to establish causation are generally accepted in the scientific community." Parker v. Mobil Oil Corp. , 7 NY3d 434, 448 (2006).
The Parker Court noted that there are other ways an expert might demonstrate specific causation, e.g., estimating exposure through the use of "mathematical modeling." Id., at 449. However, as the Cornell Court observed, "Parker by no means...dispensed with a plaintiff's burden to establish sufficient exposure to a substance to cause the claimed adverse health effect." Cornell , 22 NY3d at 784. Moreover, as the Cornell Court also ruled, the absence of evidence of specific causation cannot be overcome via a differential diagnosis:
[T]he Appellate Division is incorrect to the extent that it suggests that performance of a differential diagnosis establishes that a plaintiff has been exposed to enough of an agent to prove specific causation. This is not what we meant when we stated that ‘precise quantification’ of exposure was not necessary, and there exist alternative ‘potentially acceptable ways to demonstrate [specific] causation’ ( Parker , 7 NY3d at 448, 449 )."
Id. , at 785.
The deficiencies in Plaintiff's showing are manifold.
First, the air quality testing provided only a "snapshot" of conditions existing in the apartment at the tail end of JL's tenancy. Plaintiff provided no basis for inferring that she was continuously exposed to a high level of airborne Aspergillus spores throughout that tenancy. Perhaps more importantly, Plaintiff did not demonstrate that she was exposed to mold at levels approximating agricultural / industrial exposures. As set forth in AAAAI (2006):
Total fungi spores that are greater in concentration in indoor than outdoor air might be potential evidence of increased fungal presence indoors. However, in normal indoor environments xerophillic fungi, such as ASP and PEN species, might be found indoors at levels above those measured outdoors on a given day. Even when the fungal levels are greater indoors than those outdoors, health risks would be limited in most cases, except to the subject specifically allergic to the mold in question. Absolute fungal spore levels indoors can be put into context when one realizes that outdoor levels can reach tens of thousands of fungal spores per cubic meter and hundreds of thousands per cubic meter or higher around rotting vegetation compost or in agricultural settings, such as in grain elevators ." (331)
The airborne fungal spores measured in JL's apartment did not even remotely approach the "hundreds of thousands per cubic meter or higher" that are found in agricultural environments.
Second, Plaintiff asserts without any meaningful proof that her exposure was intensified because she regularly exercised on the treadmill in a room where she was exposed to Aspergillus spores. As a matter of common sense, that may be true, but it does not satisfy Parker's requirement that "whatever methods an expert uses to establish causation are generally accepted in the scientific community." Id. , 7 NY3d at 448. Plaintiff made no attempt whatsoever, via mathematical modeling, biophysical evidence or otherwise, to quantify the degree to which the increased respiration attendant upon physical exercise would have increased her internal exposure to mold.
Third, there is no evidence whatsoever that mycotoxins were present in Defendants' home. As set forth in AAAAI (2006):
Specific molds can produce, under some conditions, a variety of myco or none at all. Thus measurements of spores cannot be used as surrogates of myco exposure . (331)
Only certain mold species produce specific mycotoxins under specific circumstances. Importantly, the mere presence of such a mold should not be taken as evidence that the mold was producing any mycotoxin. For a toxic effect to occur in a subject, (1) the toxin must be present, (2) there must be a route of exposure, and (3) the subject must receive a sufficient dose to have a toxic effect . In the nonoccupational setting the potential route of exposure is through inhalation. Mycotoxins are not volatile and, if found in the respirable air, are associated with mold spores or particulates. They are not cumulative toxins, having half-lives ranging from hours to days depending on the specific mycotoxin . Calculations for both acute and subacute exposures on the basis of the maximum amount of myco found per mold spore for various myco and the levels at which adverse health effects are observed make it highly improbable that home or office myco exposures would lead to a toxic adverse health effects ." (329)
Here, there was no measurement of mycotoxins, if any, present in Defendants' home. Neither were the Aspergillus or Stachybotrys mold spores found therein tested to determine whether they were producing, or could produce, mycotoxins, and if so in what amount. Nor was any attempt made, via mathematical modeling or otherwise, to extrapolate from the air quality test results to a putative quantum of inhaled mycotoxins.
Fourth, and finally, the blood and urine testing which Dr. Grant conducted does not correlate at all to JL's exposure to mold or mycotoxins in Defendants' home. AAAAI (2006) states:
Testing for IgG antibodies to mold proteins cannot be used as a surrogate to assess either the level or timing of specific mold exposures. This is not surprising given the widespread occurrence of molds in the environment . (330-331)
Moreover, Dr. Grant explicitly admitted:
Q Dr. Grant, is there a way to tell from the blood test that you took, and the urine test that you took, whether or not a mycotoxin or Trichothecene was present because of consumption via food or because of inhalation?
A No. (418)
Hence, even assuming that an exposure to mold and/or mycotoxins at a certain level is capable of causing a particular illness or illnesses as claimed by Dr. Grant, Plaintiff has wholly failed to demonstrate that she was exposed to sufficient levels of the toxin to cause those illnesses, and has therefore failed to prove specific causation.
C. Differential Diagnosis
Differential diagnosis "assumes that general causation has been proven." Cornell, supra , 22 NY3d at 785. Moreover, the performance of a differential diagnosis cannot establish that a plaintiff has been exposed to enough of an agent to prove specific causation. See, id. For the reasons shown above, Plaintiff has established neither general nor specific causation, and hence, as a matter of law, Dr. Grant's differential diagnosis of JL is incapable of establishing causation.
However, assuming arguendo that general and specific causation were established, Plaintiff remains obligated to demonstrate that Dr. Grant's differential diagnosis was properly performed. "[D]ifferential diagnosis ‘requires physicians to both ‘rule in’ and ‘rule out’ the possible causes of the patient's symptoms through accepted scientific reasoning and diagnostic tests." Cornell, supra , 22 NY3d at 785. Dr. Grant frankly acknowledged that the means by which she diagnosed JL with Aspergillosis were not generally accepted in 2011. (68) Plaintiff has failed to substantiate Dr. Grant's claim that those means are generally accepted now.
The primary bases for Dr. Grant's diagnosis were as follows:
1. The Air Quality Testing of JL's Apartment
As set forth in the discussion of "Specific Causation" above, Plaintiff failed to establish via the air quality testing or any other evidence that she was exposed to sufficient levels of mold or mycotoxin to cause the illnesses diagnosed by Dr. Grant.
2. JL's Gilbert's Syndrome and MTHFR Gene
In her March 2017 expert report (5, 12) and in her July 2018 affirmation (IG Aff. ¶¶ 12, 26, 31[b] ), Dr. Grant opined that JL was predisposed and vulnerable to toxin-induced tissue injury and to infection on account of her Gilbert's Syndrome and MTHFR defect. Dr. Phillips testified that Gilbert's Syndrome affects excretion; that mycotoxins are broken down chemically, not excreted; and hence, that Gilbert's Syndrome does not affect detoxification or the half-lives of toxins in the body. (MP 39-40) Dr. Phillips further testified, regarding the MTHFR gene, that JL had a "heterozygous mutation" (found in 50% of all people) which had no impact on her detoxification capacity. Even coupled with Gilbert's Syndrome, it had no impact on her susceptibility to mold and no correlation to mold-related disease. (MP 42-43, 52, 57, 655)
In the face of Dr. Phillips' testimony, Plaintiff abandoned all reliance on Dr. Grant's contention regarding JL's Gilbert's Syndrome and MTHFR gene in her Post-Frye Hearing Brief.
3. The Presence of Ochratoxin in Resected Sinus Tissue From JL's December 2010 Sinus Surgery
Since mold is ubiquitous, many people have mold in their sinuses, especially persons like JL with a history of sinusitis and resection. The presence in JL's sinus of ochratoxin, a metabolite of Aspergillus, is certainly indicative of the presence of mold, but, as Dr. Grant and Dr. Phillips agreed, the sinuses are outside the body, and real infection occurs only when the mold invades the tissues of the body. (IG 40; MP 554-556, 607, 661)
4. JL's Elevated A. Fumigatus IgG Titer in May 2011
AAAAI (2006) states:
Generally, host factors, rather than environmental exposure, are the critical factor in the development of opportunistic mold infection in immunocompromised individuals because exposure to potential fungal opportunistic pathogens (eg, ASP species) is ubiquitous in normal outdoor and indoor environments. Accepted histological and microbiologic methods should be used to make the diagnosis of fungal infection . (328)
AAAAI (2006) further states:
Measurement of IgG antibodies to mold proteins . Assessment of IgG antibodies to mold proteins can be performed through immunoprecipitation-double diffusion or solid-phase immunoassays. Such testing has demonstrated value in assessment of individuals with suspected HP or allergic bronchopulmonary mycosis . Such testing (immunoprecipi-tation or solid-phase IgG testing) is appropriate to perform only in the setting of a clinical picture, including history, physical examination, imaging studies, and other laboratory assessments, suggesting HP or allergic bronchopulmonary mycosis as part of the differential diagnosis . Use of these tests as screening procedures for these diseases in the absence of an appropriate clinical picture is discouraged.
Immunoprecipitation testing remains the standard approach because the presence of precipitating antibodies is strong supportive evidence in the appropriate clinical setting. However, as many as half of highly exposed individuals might have precipitating antibodies in the absence of any clinical disease . (330-331)
Plaintiff did not demonstrate that Dr. Grant employed "accepted histological and microbiologic methods" in diagnosing fungal infection. Moreover, while the measurement of IgG antibodies has "demonstrated value in assessment", it is only "supportive evidence in the appropriate clinical setting" because many highly exposed individuals have "precipitating antibodies in the absence of any clinical disease." As Dr. Phillips explained, elevated IgG titers demonstrate exposure to mold, but "you can't use the antibodies to tell you when the mold exposure occurred, how intensely the mold exposure occurred, what the source of the mold exposure was, and what implications of that mold exposure is on human disease." (MP 575-576)
At the Frye hearing, Plaintiff relied on a number of more recent scientific articles by David Denning, a recognized expert on Aspergillosis, concerning the role of IgG titers in diagnosing mold infection. (See, Tabs 22, 37, 43, 45, 46) While these studies demonstrate that there have been scientific advances in defining the diagnostic criteria for various forms of Aspergillosis, it remains the case that elevated IgG titers are only supportive evidence and not themselves diagnostic of mold infection. Page, Denning et al., Antibody testing in aspergillosis -- quo vadis? (2015) (Tab 45), is representative. As set forth hereinabove:
In this review article, the authors begin by observing: "Humans are constantly exposed to airborne Aspergillus spores. Most develop Aspergillus-specific antibodies by adulthood. Persons with chronic lung disease or Aspergillus airway colonization often have raised levels of Aspergillus-specific immunoglobulin G (IgG). It is not known whether this signifies an increased risk of future aspergillosis ." (417) Since "[t]he antibody response to Aspergillus and thus the role of antibody measurement in diagnosis and management varies greatly from one syndrome to another" (418), the authors consider the role of antibody testing in diagnosing various forms of aspergillosis.
"The vast majority of patients with aspergillosis have one or more underlying disorders and the presentation of aspergillosis varies in line with the underlying disorder." (418) The syndrome most closely approximating Dr. Grant's diagnosis of JL the authors describe as a form of "sub-acute invasive pulmonary aspergillosis" called "chronic invasive fungal rhinosinusitis." The authors write: "[S]ub-acute invasive pulmonary aspergillosis ] is normally seen in patients with mild immunosuppression due to diabetes, steroid use, alcoholism, COPD, tuberculosis or AIDS. A similar condition occurs in the sinuses, where it is termed chronic invasive fungal rhinosinusitis. Diagnosis of sub-acute invasive aspergillosis is based on a combination of symptoms, radiological changes and laboratory tests, including antibody and antigen tests or culture ." (419)
In sum, elevated IgG titers are of value in the assessment of possible mold-related injury, but they are not in themselves diagnostic of aspergillosis or mold infection, and their significance is highly dependent on the larger clinical picture.
5. The Presence of Ochratoxin and Trichothecenes in JL's Urine In May 2011
In May 2011, the presence -- unquantified -- of ochratoxin and trichothecenes was detected in JL's urine. In 2015, the CDC reported: "Mycotoxins are metabolites of some fungi that can cause illness in humans and animals, primarily after ingestion of contaminated foods. Low levels of mycotoxins are found in many foods; therefore, mycotoxins are found in the urine of healthy persons. Mycotoxin levels that predict disease have not been established. Urine mycotoxin tests are not approved by FDA for accuracy or for clinical use ." Kawamoto et al., Use of Unvalidated Urine Mycotoxin Tests for the Clinical Diagnosis of Illness (2015).
Dr. Phillips testified further that the ACOEM, AAAAI, WHO and European Union have issued admonitions stating that urine testing for mycotoxins should not be performed because these toxins are usually present in the urine of healthy persons and do not correlate with human disease. (MP 577, 592-594, 611) Plaintiff has proffered no literature reflecting the general acceptance of urine testing as a diagnostic tool for mold-related disease.
6. JL's Objective Neurological Symptoms
As noted above, differential diagnosis requires physicians to "rule out" other possible causes of the patient's symptoms through accepted scientific reasoning and diagnostic tests." Cornell, supra, 22 NY3d at 785. JL treated with a number of physicians besides Dr. Grant, none of whom attributed JL's symptoms to mold, and one of whom suspected a possible "conversion disorder," i.e., that JL's neurological condition was psychogenic in origin.
When asked if she had ruled out the possibility of a psychogenic disorder to account for her neurological condition, Dr. Grant testified:
A Of course psychogenic is something to consider. In her case, it's not even on the differential diagnosis .
Q Why is it not on the differential diagnosis?
A Because she had objective findings.
Q What was the objective finding?
A She had to have a brace. She really had real neurological symptoms. (IG 350)
However, as Dr. Phillips observed, the very definition of a conversion disorder is one which is psychological in origin but physical in manifestation (MP 613, 668), which can be ruled out only via psychogenic testing which Dr. Grant was unqualified to perform, and for which she never referred JL. (MP 668-669) Dr. Grant's testimony that JL's "objective findings" obviated the need to rule out a psychogenic condition or conversion disorder is patently incorrect.
Summing up, the foundation for Dr. Grant's differential diagnosis of mold-related disease is problematic in each and every respect. The air quality testing of JL's apartment did not demonstrate sufficient exposure to mold or mycotoxins to cause serious mold-related illness.
Dr. Grant's reliance on the purported impairment of JL's ability to clear toxins and consequent vulnerability to infection was ill-founded and abandoned upon the Frye hearing. The presence of mycotoxins in JL's sinuses, "outside" of the body, and her urine is commonplace and does not correlate with human disease. The elevated IgG titer was indicative of mold exposure, and potentially supportive of a diagnosis, but not in itself diagnostic of illness in the absence of primary evidence of infection. Dr. Grant acknowledged that her methodology was not generally accepted in 2011 -- and Plaintiff has not demonstrated that it would be acceptable today -- notwithstanding which she placed JL on a regime of anti-fungal medication and proffers JL's response to this therapy as proof of the accuracy of her diagnosis. To that we now turn.
7. JL's Purported Improvement on a Regime of Anti-Fungal Medication
Dr. Grant placed JL on a regime of anti-fungal medication including oral itraconazole and topical naso/oral/GI amphotericin, which, per Dr. Grant, resulted in a "marked improvement" of her symptoms. JL maintained this treatment for approximately three months before another physician stopped it and prescribed antibiotics and steroids, whereupon, again per Dr. Grant, JL relapsed and all symptoms, especially rhinosinus and neurological, returned. (IG Aff. Par. 18-19) Dr. Grant further states, "A recurring pattern has been her consistent improvement while on antifungal treatment and her consistent decline when she has had to stop such treatment due to financial/insurance constraints or by other doctor's orders." (IG Aff., Par. 20) Plaintiff proffers this as evidence supporting the accuracy of Dr. Grant's diagnosis. However, as Dr. Phillips points out, "it is not empirically obvious in the medical record that her symptoms were waxing and waning objectively. Subjectively she [i.e., Dr. Grant] has made those statements, but objectively the data does not support it." (MP 663) Plaintiff has made no effort to substantiate Dr. Grant's assertions by correlating them with the history documented in the medical records.
Dr. Phillips acknowledged that if a patient had an infection related to mold, and the mold was actively proliferating in the body, then an appropriate response to anti-fungal therapy would be useful in determining causation; otherwise, not. (MP 603) Dr. Phillips forcefully rejected Dr. Grant's assertion that the standard of care for managing fungal infections is empiric:
That's absolutely not true. It's like saying I don't know what it is, so I'm going to throw an answer at it. You do not do empiric treatments of patients if they're not justified. If you do treat a patient, one of three things could happen. You could be right, and...you help the patient. You can give it and it's superfluous and it doesn't do anything one way or the other. Or you could be wrong and you could harm the patient.
If you start giving patients empiric Amphotericin, which is a known hepatotoxin, or other antifungal agents, you're more likely than not going to cause a problem, you're going to suppress the patient, and you're going to cause the issues rather than helping them.
...my job as lead clinical physician for the department of medicine is to make sure that we don't do this. We base our decision on evidence And if the evidence indicates that that's the proper diagnosis you act on it. If the evidence isn't there, then you don't act on it.
Empiric observation is very misleading. It's like saying I made a mistake before, now I'm gonna make that mistake again and I continue making that mistake. That [is] what happens with empiric observations. And that's why for so many years medical science did not advance. The whole idea is to get rid of these empiric observations and base our decisions on facts." (MP 659-660)
It is for precisely these reasons that Judge Battaglia characterized Dr. Grant's method -- "treat[ing] individuals identified as having ‘significant heavy mold exposure’ with anti-fungal therapy, and track[ing] the results, concluding that ‘removal of the fungi removes the trouble’ " -- as an observational study or case report which is "not generally accepted in the scientific community on questions of causation." See, Rosati v. Brigham Park Co-op. Apartments, Sec. No. 2, Inc., supra, 36 Misc 3d 1214(A) at *15. Furthermore, inasmuch as the purported connection between JL's use of anti-fungal medication and an improvement of her symptoms is grounded solely on Dr. Grant's say-so and not on detailed analysis of the documented medical history, this is a classic instance of "too great an analytical gap between the data and the opinion proffered" because the expert's opinion "is connected to existing data only by the ipse dixit of the expert." See, People v. Brooks, supra, 31 NY3d at 941 ; Cornell, supra , 22 NY3d at 781.
D. Conclusion
In view of the foregoing, the Court grants Defendants' application to preclude the testimony of Dr. Irene Grant, and Dr. Grant is hereby precluded from testifying at the trial of this action except as to the "minor respiratory ailments" which Defendants have acknowledged could potentially have been the product of JL's exposure to mold on their premises. (4)