Chronic Interstitial Lung Disease in Nylon Flocking Industry Workers -- Rhode Island, 1992-1996

Interstitial lung disease (ILD) occurs infrequently; some cases are attributed to sarcoidosis, pulmonary hemorrhage syndromes, connective tissue diseases, hypersensitivity pneumonitis, drugs, radiation, and mineral dusts (e.g., silica or asbestos). However, most cases of ILD are of uncertain classification or etiology (1). This report describes preliminary findings of the investigation in Rhode Island of an outbreak of ILD among workers involved in the manufacture of finely cut nylon (flock) and flocked fabric (used for upholstery, clothing, and automobiles); the findings provide evidence of a newly recognized occupational illness. Description of Index Cases

In November 1994, a 35-year-old textile worker was referred to a university-based occupational health clinic for evaluation of chronic ILD. No workplace exposures were initially identified as causing his illness, and during the following 12 months, he recovered almost completely while remaining out of work and receiving systemic cortico-steroids. In January 1996, a 28-year-old man was referred to the clinic for evaluation of biopsy-confirmed ILD, characterized by bronchiolocentric nodular and diffuse interstitial lymphoid infiltrates and mild interstitial fibrosis that met histologic criteria for nonspecific interstitial pneumonia (NSIP) (2). Both men worked at the same nylon flocking plant in Rhode Island; further inquiry revealed that at the company's plant in Canada, five cases of ILD had been diagnosed during 1990-1991 (3), and two cases had been diagnosed in 1995. In March 1996, at the request of the company and with the cooperation of the workers' union, investigations were undertaken by the Brown University Program in Occupational Medicine and CDC's National Institute for Occupational Safety and Health (NIOSH). Medical/Epidemiologic Investigation

To identify additional ILD cases among current production workers (n=127) at the Rhode Island plant, all employees with persistent respiratory symptoms were encouraged to undergo full pulmonary function testing, chest radiography, and high resolution computerized chest tomography (HRCT). Those with unexplained restrictive lung function, impaired diffusing capacity, or HRCT findings consistent with ILD were referred for transbronchial or wedge biopsy. A single pulmonary pathologist reviewed all specimens as well as those of the five case-patients in Canada who had biopsies. A case of "flock-worker's lung" was defined as 1) a histologic diagnosis of NSIP (2) characterized by bronchiolocentric nodular and diffuse interstitial lymphoid infiltrates and nonuniform alveolar filling by macrophages, with or without interstitial fibrosis; 2) other histologic manifestations of ILD not attributable to another disease; or 3) in the absence of a tissue specimen, a grossly abnormal distribution of cell types on bronchoalveolar lavage (BAL) with restrictive lung function and HRCT findings of either diffuse ground glass opacity or micronodularity.

The study cohort included all current and former production workers employed at the Rhode Island facility on or after June 15, 1990, and who had worked for greater than or equal to 18 months before September 15, 1996 (n=165). * After working 18 months, cohort members contributed person-years at risk for time subsequently worked from June 15, 1990, through September 15, 1996. General population estimates for age- and sex-specific incidence of pulmonary fibrosis/idiopathic pulmonary fibrosis (PF/IPF) and for sex-specific incidence of all ILD were obtained from an ILD registry for Bernalillo County, New Mexico (1) **; using these estimates and weights based on the demographics of the study cohort, standardized incidence ratios for PF/IPF *** and for all ILD were calculated. Ninety-five percent confidence intervals (CIs) for these estimates were derived by exact Poisson calculations.

Among the 165 members of the cohort, seven (4%) were identified with "flock-worker's lung." The mean age for these seven was 41 years (range: 28-57 years); six were men. Two were current smokers, four had discontinued smoking greater than or equal to 18 months before diagnosis, and one had never smoked. ILD had been diagnosed in these persons in 1992 (one), October 1994 (one), December 1995 (one), and April-September 1996 (four). The median latencies from time of hire to onset of symptoms (gradually progressive dry cough and dyspnea) and from onset of symptoms to time of diagnosis were 6 years (range: 9 months-31 years) and 1 year (range: 4 months-4 years), respectively. Two workers reported worsening symptoms while at work, but no job category or department was associated with illness. Serologic test results (rheumatoid factor, antinuclear antibody, and hypersensitivity pneumonitis precipitins) were normal except for nondiagnostic findings in two workers. Case-patients experienced symptomatic, radiographic, and functional improvement within weeks to months of leaving work; two received corticosteroids, one remained dependent on supplemental oxygen for an additional 3 years, and none have recovered completely.

Tissue obtained from transbronchial (n=2) and wedge (n=4) biopsies demonstrated NSIP in five patients and bronchiolitis obliterans organizing pneumonia (BOOP) in the sixth. All six had nodular lymphoid infiltrates; four had germinal centers. The seventh case was diagnosed based on a BAL finding of 40% eosinophils, moderate restrictive lung function, and grossly abnormal HRCT. All of the biopsies from the five case-patients in Canada revealed NSIP; two also showed dominant areas of diffuse alveolar damage, and three revealed lymphoid nodules with germinal centers. No granulomas (suggesting hypersensitivity pneumonitis) or birefringent particles (suggesting certain pneumoconioses) were observed in any of the histologic specimens.

At the Rhode Island plant, the crude incidences of "flock-worker's lung" and of all ILD (including two cases of talcosis and one case of pulmonary histiocytosis X) were 10.5 cases per 1000 person-years and 15 cases per 1000 person-years, respectively. The standardized incidence ratios for PF/IPF and for all ILD were 258 (95% CI=104-530) and 48 (95% CI=23-88), respectively. Environmental Investigation

In flock manufacture, nylon thread previously impregnated with a titanium dioxide delusterant is dyed, coated (with a finish consisting of tannic acid, an ammonium ether of potato starch, and fatty alcohol derivatives), cut, dried, and bagged. Flocked fabric is made by using the flock's electrostatic charge to place the flock on acrylic adhesive-covered cotton-polyester fabric, which is then heat-cured. Exposures generic to the industry include bioaerosols, nylon fiber greater than or equal to 12 u in diameter, a finishing agent, acrylic adhesive, nonfibrous zeolite, heat transfer oil, and thermal degradation products. Preliminary air sampling at the Rhode Island plant, collected volumetrically, revealed extremely high short-term total dust concentrations (up to 83 mg/m3), only modest concentrations of fungal spores and endotoxin, low levels of volatile organic compounds, and negligible concentrations of metals. Respirable dust, characterized by both phase contrast microscopy and scanning electron microscopy with energy dispersive x-ray analysis, consisted of particles with physical structure and chemical composition similar to those of bulk samples of the finish components; a substantial number of respirable-size fragments of nylon also were present.

Reported by: DG Kern, MD, KTH Durand, MHS, RS Crausman, MD, A Neyer, MD, C Kuhn III, MD, Brown Univ School of Medicine, Providence; RR Vanderslice, PhD, Rhode Island Dept of Health. MD Lougheed, MD, DE O'Donnell, MD, PW Munt, MD, Queens' Univ, Kingston, Ontario, Canada. Div of Respiratory Disease Studies, National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: The findings in this report document an excessive incidence at two North American nylon flock production/flocking plants of a chronic diffuse ILD. The clinical and pathologic features of "flock-worker's lung" lack characteristics typically associated with previously recognized forms of occupational ILD (including hyper-sensitivity pneumonitis; pneumoconioses like silicosis or asbestosis; and those cases of BOOP that have followed acute massive exposure to a toxic gas, fume, or vapor) and indicate the occurrence of a previously unrecognized occupational illness.

The cause of the illness described in this report remains unknown. Although investigators of the ILD outbreak in Canada postulated an etiologic role for mycotoxins (3), no mycotoxins were detected at that plant, and two new cases of ILD occurred there after interventions were introduced to minimize mold growth; in addition, mycotoxin exposure has not been shown to cause chronic diffuse ILD. The findings in this report indicate a potential role for nylon flock and its finish in causing illness. Although intact nylon flock fibers are not considered respirable (i.e., they are too large to reach the respiratory bronchioles and gas-exchange units of the lung), preliminary evidence suggests that respirable-size nylon fragments are generated in this industry. This finding may have important implications because nylon is a polyamide, as are the agents recently implicated (4) in outbreaks of fatal BOOP among textile-dye sprayers in Spain and Algeria (5,6); furthermore, the biopsy specimens from one case-patient in Rhode Island revealed BOOP, and the index case-patient who did not have a biopsy had clinical findings that strongly suggested BOOP. Although the limited toxicologic data available for nylon and the three-component finish suggest the possibility that these substances may have adverse pulmonary effects (7-9), their role, if any, in causing "flock-worker's lung" has not been determined.

The two clusters described in this report together constitute the largest unexplained continuing outbreak of nongranulomatous chronic diffuse ILD in adults under investigation by CDC. Aspects of the illnesses of particular concern are the frequently subtle clinical, pulmonary function, and radiographic abnormalities; the potential for rapid clinical progression; and the apparent lack of complete reversibility. Until the specific cause of the outbreak is identified and eliminated, employers should ensure that work practices, engineering controls, and respirators are used to reduce respiratory exposures within the industry. Medical screening and surveillance should be intensified, and removal from exposure through alternative work or other accommodation should be offered to affected employees. CDC has initiated a series of toxicologic studies and is considering additional epidemiologic investigation within the flocking industry. Information concerning additional cases of ILD among workers employed in this industry can be reported to CDC's Epidemiological Investigations Branch, Division of Respiratory Disease Studies, NIOSH, telephone (304) 285-5751.

References

1. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 1994;150:967-72.

2. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis: histologic features and clinical significance. Am J Surg Pathol 1994;18:136-47.

3. Lougheed MD, Roos JO, Waddell WR, Munt PW. Desquamative interstitial pneumonitis and diffuse alveolar damage in textile workers: potential role of mycotoxins. Chest 1995;108:1196-200.

4. Clottens FL, Verbeken EK, Demedts M, Nemery B. Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: intratracheal administration in hamsters. Occup Environ Med 1997;54:376-87.

5. Moya C, Anto JM, Newman Taylor AJ, and the Collaborative Group for the Study of Toxicity in Textile Aerographic Factories. Outbreak of organising pneumonia in textile printing sprayers. Lancet 1994;344:498-502.

6. Ould-Kadi F, Mohammed-Brahim B, Fyad A, Lellou S, Nemery B. Outbreak of pulmonary disease in textile dye sprayers in Algeria {Letter}. Lancet 1994;344:962-3.

7. Pimentel JC, Avila R, Lourenco AG. Respiratory disease caused by synthetic fibres: a new occupational disease. Thorax 1975;30:204-19.

8. Rohrbach MS. Modulation of alveolar macrophage function by condensed tannin. Am J Ind Med 1994;25:97-9.

9. Hollander A, Heederik D, Kauffman H. Acute respiratory effects in the potato processing industry due to a bioaerosol exposure. Occup Environ Med 1994;51:73-8.

* The company's recordkeeping system precluded formation of a larger cohort and necessitated the 18-month employment requirement. 

** These data from Bernalillo County represent the only available estimates of background incidence of ILD cases. For the category of "all ILD," only sex-specific rates are available. 

*** Background rates of PF/IPF were used to derive the standardized incidence ratio because cases of "flock-worker's lung" probably would have been relegated to this broader ILD subcategory had the apparently specific clinicopathologic picture and occupational association been overlooked.

+------------------------------------------------------------------- -+ | Erratum: Vol. 46, No. 38 | |             | | In the article "Chronic Interstitial Lung Disease in Nylon | | Flocking Industry Workers -- Rhode Island, 1992-1996," on page 900,| | in the first line of the credits a name was misspelled. The name | | should be A Nayer, MD. | |             | +------------------------------------------------------------------- -+-

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