Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

Beckett, William S.; Kallay, Michael C.; Sood, Akshay; Zuo, Zhengfa; Milton, Donald K.

doi:10.1289/ehp.7727

Cited by 62 publications

(38 citation statements)

References 24 publications

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“…Although asthma and dermatitis seem to be caused by the chemical toxicity of MWFs due to additional components (e.g., biocides, defoamers, corrosion inhibitors, or dyes) (22,33,38), MOL has been related to microorganisms that frequently contaminate MWFs, especially Mycobacterium immunogenum, a recently described, fast-growing mycobacterium included in the Mycobacterium chelonae-Mycobacterium abscessus complex (18,24,37,48,52,54). Arguments in favor of this etiology are the presence of specific precipitins in MWF-related HP cases (5,14,32) and/or the presence of M. immunogenum in their environment (4,18,42,52). The ability to induce HP in mice exposed intranasally to M. immunogenum (16,40) is evidence of the role of this microorganism.…”

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confidence: 99%

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Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung

Murat

Grenouillet

Reboux

et al. 2012

Appl Environ Microbiol

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Hypersensitivity pneumonitis, also known as "machine operator's lung" (MOL), has been related to microorganisms growing in metalworking fluids (MWFs), especially Mycobacterium immunogenum. We aimed to (i) describe the microbiological contamination of MWFs and (ii) look for chemical, physical, and environmental parameters associated with variations in microbiological profiles. We microbiologically analyzed 180 MWF samples from nonautomotive plants (e.g., screw-machining or metalcutting plants) in the Franche-Comté region in eastern France and 165 samples from three French automotive plants in which cases of MOL had been proven. Our results revealed two types of microbial biomes: the first was from the nonautomotive industry, showed predominantly Gram-negative rods (GNR), and was associated with a low risk of MOL, and the second came from the automotive industry that was affected by cases of MOL and showed predominantly Gram-positive rods (GPR). Traces of M. immunogenum were sporadically detected in the first type, while it was highly prevalent in the automotive sector, with up to 38% of samples testing positive. The use of chromium, nickel, or iron was associated with growth of Gram-negative rods; conversely, growth of Gram-positive rods was associated with the absence of these metals. Synthetic MWFs were more frequently sterile than emulsions. Vegetable oil-based emulsions were associated with GNR, while mineral ones were associated with GPR. Our results suggest that metal types and the nature of MWF play a part in MWF contamination, and this work shall be followed by further in vitro simulation experiments on the kinetics of microbial populations, focusing on the phenomena of inhibition and synergy.

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confidence: 99%

“…Since the first reports (5,27), most described cases of MWFrelated HP have been in the U.S. automotive industry (4,18,20,24,28,32,37,42,56). The first European case clusters were recently reported in automotive plants in Great Britain (8) and in France (41).…”

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confidence: 99%

Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung

Murat

Grenouillet

Reboux

et al. 2012

Appl Environ Microbiol

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“…described 12 cases (2003-2004) of MWF-associated HP who had precipitins against Acinetobacter and Ochrobactrum, but precipitins were also present in a similar proportion of exposed control workers without disease at the same plant. Many of MWF-associated HP cases were linked to MWF containing nontuberculous RGM [21,24,[27][28][29]. WILSON et al [4] and WALLACE et al [24] showed that 95% of mycobacterial isolates recovered from industrial MWF in plants with cases of machinist HP belong to M. immunogenum.…”

Section: Subjectsmentioning

confidence: 99%

Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria

Tillie‐Leblond¹,

Grenouillet²,

Reboux³

et al. 2010

European Respiratory Journal

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Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers.13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWFassociated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum.M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established.The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.

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“…HP is caused by the inhalation of a wide variety of antigenic particles small enough to reach the alveoli, comprised of microbial, animal, or insect proteins and other constituents. Environmental mycobacteria of the M. chelonae-M. abscessus (MCA) group -particularly M. immunogenum -have been associated with outbreaks of HP in factory workers inhalationally exposed to contaminated metalworking fluid (MWF) aerosols (Kreiss & Cox-Ganser 1997;Moore et al 2000;Wilson et al 2001;Falkinham 2003;Beckett et al 2005;Tillie-Leblond et al 2011). HP cases presenting variable clinical forms (acute, subacute, chronic) have been observed in machinists exposed to contaminated MWF (Freeman et al 1998;Zacharisen et al 1998;Beckett et al 2005;Rosenman 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Environmental mycobacteria of the M. chelonae-M. abscessus (MCA) group -particularly M. immunogenum -have been associated with outbreaks of HP in factory workers inhalationally exposed to contaminated metalworking fluid (MWF) aerosols (Kreiss & Cox-Ganser 1997;Moore et al 2000;Wilson et al 2001;Falkinham 2003;Beckett et al 2005;Tillie-Leblond et al 2011). HP cases presenting variable clinical forms (acute, subacute, chronic) have been observed in machinists exposed to contaminated MWF (Freeman et al 1998;Zacharisen et al 1998;Beckett et al 2005;Rosenman 2009). While there has been increasing interest in both clinical and research aspects of MWF-associated HP (Gupta et al 2009;Tillie-Leblond et al 2011;Roussel et al 2011;Burton et al 2012;Chandra et al 2013Chandra et al , 2015, differential diagnosis and immunological mechanisms of this occupational lung disease are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice

Johansson

Boivin

Yadav

2017

Journal of Immunotoxicology

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Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose-and timedependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro-(TNFa, IL-6, IL-1b) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes <5% at all timepoints or concentrations. Granulomatous inflammation peaked between 8 and 24 h post-exposure, and resolved by 96 h. Live bacterial challenge, typically encountered in real-world exposures, showed no significant differences from bacterial lysate except for induction of appreciable levels of interferon (IFN)-c, implying additional immunogenic potential. Collectively, the short-term mycobacterial challenge in mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter-and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease. ARTICLE HISTORY

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Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

Cited by 62 publications

References 24 publications

Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung

Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung

Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria

Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice

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