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Biopsy-Confirmed Hypersensitivity Pneumonitis in Automobile Production Workers Exposed to Metalworking Fluids -- Michigan, 1994-1995

In 1994, union and management officials and local physicians in southeastern Michigan noted the occurrence among automobile production workers of respiratory illness consistent with hypersensitivity pneumonitis (HP). Local and national health authorities reviewed medical records, and in June 1994, individual employees and the union requested that CDC's National Institute for Occupational Safety and Health (NIOSH) evaluate potential occupational exposures associated with these illnesses. This report summarizes preliminary findings of the evaluation, including detailed information about one HP case and a summary description of the six biopsy-confirmed cases among automobile production workers from three different plants (plants A, B, and C) in southeastern Michigan; all six workers had jobs that entailed frequent exposure to metalworking fluids (MWFs). The findings suggest the need for further evaluation of a possible association of occupational exposure to MWFs with HP. Case Report

In February 1994, a 57-year-old man (patient 1) was evaluated for a 7-month history of wheezing, dyspnea, weight loss, fever, and productive cough. He had worked as a toolmaker at plant A for 11 years and had not smoked cigarettes for the preceding 28 years. His symptoms were temporally related to working in an area of the plant where soluble machining oils -- a type of MWF -- were used. The worker's respiratory illness progressed, and in May, he was hospitalized for acute respiratory failure. Findings on admission included basilar inspiratory crackles, and a chest radiograph indicated bilateral interstitial infiltrates. Oxygen tension on room air at rest was 53 torr (normal: 80-100 torr) with 82% saturation; a white blood cell count was 11,900 (normal: 4800-10,800) with a normal differential. Fiberoptic bronchoscopy and examination of tissue specimens obtained by transbronchial biopsies demonstrated multiple noncaseating granulomas with lymphocytic infiltration of the alveolar septa -- findings consistent with HP.

Following diagnosis of HP, the patient was treated with oral corticosteroids and was removed from work for medical reasons. Pulmonary function tests (PFTs) obtained in May indicated a forced vital capacity of 3.8 L (75% of predicted; normal: greater than 80% predicted), total lung capacity (TLC) of 5.7 L (79% of predicted; normal: greater than 80% predicted), and diffusing capacity for carbon monoxide (DLCO) of 18.79 (67% of predicted; normal: greater than 80% predicted). Subsequent PFTs obtained in March 1995 showed a normal TLC (6.9 L {93% of predicted}) and DLCO (24.85 {89% of predicted}). Case Summaries

During 1994-1995, physicians at two local pulmonary and occupational medicine clinics in Michigan reported four cases of biopsy-confirmed HP (including patient 1) among workers from three different automotive plants. A subsequent review of the medical records of plant employees who had sought medical attention identified two additional biopsy-confirmed cases. In addition, 14 probable cases (not biopsy-confirmed) were identified.

All six persons with biopsy-confirmed cases (Table_1) were nonsmokers for at least 12 years preceding illness. All except one reported recurrent respiratory and systemic symptoms that were temporally related to working in areas of their respective plants in which MWFs were used: the symptoms of one worker (patient 3) resolved after he was permanently removed from the workplace for medical reasons; the symptoms did not recur. MWFs were the only potential exposures previously associated with HP to be identified by the investigation. One worker (patient 5) had a 1-1/2-year history of interstitial lung disease and work-related symptoms of dyspnea and cough; this worker died as a result of acute myocardial infarction, and autopsy findings indicated the presence of chronic granulomatous lung disease. Serum precipitins to a standard commercial antigen panel (including bacteria, fungi, and avian proteins that have been associated with HP in other settings) were negative in the two workers who were tested. Pulmonary function abnormalities among the six workers included decreased DLCO (patients 2, 5, and 6) and spirometric patterns consistent with restrictive defects (patients 1 and 2) or mixed restrictive/obstructive defects (patients 3 and 5).* Following removal from exposure to MWFs and other medical treatment, pulmonary function improved in all six workers.

Investigators are continuing evaluation of the workers at these plants, including further follow-up of the workers in whom HP was diagnosed, additional case finding, exposure assessments, and a prospective evaluation of respiratory and systemic symptoms among workers exposed to MWFs.

Reported by: C Rose, MD, Dept of Medicine, National Jewish Center for Immunology and Respiratory Medicine, and Univ of Colorado Health Sciences Center, Denver, Colorado. T Robins, MD, Dept of Environmental and Industrial Health, Univ of Michigan; P Harkaway, MD, St Joseph Hospital, Ann Arbor, Michigan. Hazard Evaluations and Technical Assistance Br, Div of Surveillance, Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: HP (also known as extrinsic allergic alveolitis) is a diffuse interstitial granulomatous lung disease thought to involve an immunologic reaction of the lung to repeated inhalation of foreign antigens. Numerous antigens have been associated with HP, including many types of bacteria and fungi, animal proteins, and low molecular weight chemicals (1). Farmer's lung, a prototypical form of HP, has been associated with exposure to thermophilic bacteria and several fungal species. Because the presence of precipitating antibodies in serum reflects past exposure to the corresponding antigens, testing serum for precipitating antibodies against suspected antigens may be included in the diagnostic evaluation for HP.

Although the findings in this report suggest a link between occupational exposure to MWFs and HP, the ability to assess a causal association is subject to at least four limitations. First, these cases may not be representative of all HP cases among workers at the three plants because cases were not identified systematically from a defined population, diagnosis of HP is difficult, and symptoms of HP mimic those of other more commonly diagnosed diseases (e.g., bronchitis or pneumonia). Second, actual exposures to MWFs were not measured. Third, this analysis did not estimate HP prevalences and incidences at the three manufacturing plants; such estimates have been calculated in specific occupationally exposed populations, but overall rates are unknown. Finally, no specific antigen(s) has been associated with these cases. Precipitating antibodies were absent in the two workers who were tested; however, this may reflect the complexity of microbial species contamination or an antigen profile in MWFs that differs from those included in standard testing panels.

NIOSH estimates that approximately 1 million U.S. workers are potentially exposed to MWFs (2). These fluids are used in a variety of industries to reduce friction between cutting tools and work surfaces and to remove material residue and heat from work surfaces during cutting or machining operations. MWFs are categorized into three major classes: straight (insoluble) oils, soluble (emulsified) oils, and synthetic fluids. The water-based fluids (soluble oils and synthetic fluids) are prone to high levels of microbial contamination, and routine use of MWFs can result in the generation of respirable aerosols (3). Exposure to MWF aerosols previously has been associated with cross-shift (i.e., during or after a work shift) decrements in airflow (a sign of reversible airway obstruction) and with cases of work-related asthma, although the precise pathophysiologic mechanisms for these associations remain unclear (4-6). HP-like illnesses associated with exposure to MWFs previously have been reported in the United Kingdom (7) and among U.S. automobile-manufacturing workers exposed to water-based MWF aerosols (8).**

The diagnosis of HP should be considered in persons with recurrent "pneumonia" or with recurrent or persistent episodes of unexplained respiratory and systemic symptoms***. Although no one factor has been identified that predicts clinical outcome, recurrent episodes of acute HP can lead to progressive, irreversible lung impairment. The primary treatment for HP is avoidance of continued antigen exposure. The severity of illness in the workers in this report, including the progression to respiratory failure in one case, emphasizes the importance of early recognition and treatment of this illness.

This report highlights the need for ongoing medical surveillance and exposure assessment for workers potentially exposed to MWFs to better characterize the suspected association between occupational exposure to MWFs and HP. The ongoing investigation of these cases includes further assessment of occupational exposures to MWFs, the nature of the inhaled antigens in workplaces in which MWFs are used, and the prevalence and natural history of HP in workers exposed to MWF aerosols.


  1. Rose C. Hypersensitivity pneumonitis. In: Rosenstock L, Cullen MR, eds. Textbook of clinical occupational and environmental medicine. Philadelphia: WB Saunders, 1994.

  2. NIOSH. Work-related lung disease surveillance report, 1994. Cincinnati, Ohio: US Department of Health and Human Services, Public Health Service, CDC, 1994; DHHS publication no. (NIOSH)94-120.

  3. Chan TL, D'Arcy JB, Slak J. Size characteristics of machining fluid aerosols in an industrial metalworking environment. Applied Occupational and Environmental Hygiene 1990;5:162-70.

  4. Kennedy AM, Walton D, Chan-Yeung M. Change in baseline responsiveness in young workers: role of baseline characteristics and machining fluid exposure {Abstract}. Am J Resp Crit Care Med 1995;151:A419.

  5. Robins TG, Seixas NS, Burge H, et al. Association of cross-shift dec rements in pulmonary function with machining fluid exposure {Abstract}. Am J Respir Crit Care Med 1995;151:A420.

  6. Eisen EA, Greaves IA. Asthma in automobile workers exposed to metal working fluids {Abstract}. Am J Respir Crit Care Med 1995;151:A421.

  7. Meredith SK, McDonald JC. Work-related respiratory disease in the United Kingdom, 1989-1992: report on the SWORD project. Occup Med 1994;44:183-9.

  8. Bernstein DI, Lummus ZL, Santilli G, Siskosky J, Bernstein IL. Machine operator's lung: a hypersensitivity pneumonitis disorder associated with exposure to metalworking fluid aerosols. Chest 1995;108:636-41.

  9. Terho EO. Diagnostic criteria for farmer's lung disease. Am J Indust Med 1986;10:329.

  10. Richerson HB, Bernstein IL, Fink JN, et al. Guidelines for the clinical evaluation of hypersensitivity pneumonitis. J Allergy Clin Immunol 1989;84:839-44.

Available information was insufficient to characterize the PFT results for patient 4. ** These workers were diagnosed with HP based on a combination of work-related symptoms, chest radiographic findings, and lung-function studies; none underwent lung biopsy to confirm the diagnosis. *** When sufficient clinical criteria for a definitive diagnosis of HP are lacking, lung biopsy may be indicated (9,10); in addition, because transbronchial biopsy may sample unrepresentative areas of the lung, thoracoscopic or open-lung biopsy may be required.

+------------------------------------------------------------------- -------+ |             | | Erratum: Vol. 45, No. 28 | |             | | SOURCE: MMWR 45(31);678 DATE: Aug 09, 1996 | |             | | In the report "Biopsy-Confirmed Hypersensitivity Pneumonitis | | in Automobile Production Workers Exposed to Metalworking Fluids -- | | Michigan, 1994-1995," reference 2 cited in the list on page 606 is | | incorrect. The correct citation should be: NIOSH. National | | Occupational Exposure Survey, 1981-1983. Cincinnati, Ohio: US | | Department of Health and Human Services, Public Health Service, | | CDC. (Unpublished data). | |             | +------------------------------------------------------------------- -------+
Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.

TABLE 1. Clinical findings for six automobile production workers* with hypersensitivity pneumonitis -- production plants A,
B and C, Michigan, 1994 1995
                                                                 Initial pulmonary function (% predicted) +
                   Job       Work-related        Physical        -------------------------------------------------------------
Patient &  Plant   title      symptoms @        examination      CXR/HRCT **      FEV1    FVC    TLC    DLCO   Biopsy
  1 ++       A   Toolmaker   Wheeze, dyspnea,  Basilar crackles  Bilateral         76      75     79     67    Noncaseating
                             cough/sputum,                       interstitial                                  granulomas
                             and weight loss                     infiltrates

  2          B   Machining   Dyspnea, chills,  Clear             Interstitial      79      74     85     41    Granulomas,
                 supervisor  fatigue,                            process/                                      lymphocytic
                             diaphoresis, and                    pulmonary                                     infiltrate
                             cough                               fibrosis

  3          B   Grinder     Cough/sputum and  Basilar crackles  Ground glass      45      61    210     90    Noncaseating
                             chills                              opacification                                 granulomas,

  4          B   Metal       Dyspnea           Basilar crackles  Decreased         D &&     D      D     NA @@ Granulomatous
                 machine     myalgias, chills,                   lung volumes;                                 interstitial
                 repair      and headache                        increased                                     pneumonitis

  5          C   Machinist   Dyspnea           Clear             Interstitial      72      94     80     44    Granulomas
                                                                 pattern;                                      at autopsy
                                                                 thickening of

  6          C   Carpenter   Cough/sputum,     Basilar crackles  Basilar           83      81     84     60    Granulomatous
                             dyspnea, and                        interstitial                                  pneumonitis
                             weight loss                         pattern
*  All workers exposed to water-based metal-working fluid aerosols during work.
+  FEV1=forced expiratory volume at one second (normal: >80% predicted); FVC=forced vital capacity (normal: >80% predicted);
   TLC=total lung capacity (normal: >80% predicted); DLCO=diffusion capacity for
   carbon monoxide (normal: >80% predicted).
&  Workers were aged 35-60 years; all were nonsmokers for at least the previous 12 years.
@  Symptoms temporally related to the workplace.
** Chest radiograph and/or high-resolution computed tomography scan of lungs.
++ Patient described in text.
&& Test result recorded only as "decreased."
@@ Records not available.

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