Miscellaneous Occupational Lung Diseases

Written By: Sam Savage

Published Date: August 13, 2008 Last Edited: August 13, 2008

By Erdogan, M Sarper Martin, Christopher J

ABSTRACT. A case is presented of a rare occupational lung disease for which the workplace etiology may have been overlooked. The authors review 4 such diseases, which are important to recognize not only because cessation of exposure can lead to clinical improvement, but also because other cases of these conditions may be identified in the workplace. KEYWORDS: occupational exposure, occupational lung disease

CASE PRESENTATION

A 33-year-old woman presents with repeated episodes of nonproductive cough, fever, fatigue, and night sweats. She has been hospitalized on several occasions and received multiple courses of antibiotics and corticosteroids without improvement. Her chest radiograph shows diffuse patchy infiltrates. An open-lung biopsy reveals findings consistent with bronchiolitis obliterons organizing pneumonia.

An occupational history reveals that the patient is employed in a cabinet manufacturing facility. Identifiable exposures include sawdust, paint and oil mists containing refined castor oil, petroleum, and linseed oil. After re-examining the biopsy specimen, the attending physician notes that lipidladen macrophages are filling the alveolar spaces. The patient improves after removal from the workplace.1

BACKGROUND

A variety of occupational lung conditions are less wellrecognized than are the classic diseases of pneumoconioses, asthma, byssinosis, and hypersensitivity pneumonitis. Frequently, these rare conditions present along the spectrum of bronchiolitis obliterans organizing pneumonia. Because this disease is often considered idiopathic, clinicians should always bear in mind the possibility of an occupational cause.

Table I summarizes the conditions we will discuss in this article. We emphasize acute diseases resulting from relatively high- level exposures; however, many of these exposure settings can also result in chronic diseases from more prolonged, lower-level exposures.

ORGANIZING PNEUMONIA IN TEXTILE PRINTING SPRAYERS

In 1992 in Valencia, Spain, an outbreak of severe interstitial lung disease occurred among factory workers employed in 8 textile- printing factories, resulting in 6 deaths.2 Because a majority of these patients were employed at a factory named Ardystil, the condition has become known as Ardystil syndrome. Among 27 heavily exposed workers, symptoms at presentation included cough (n = 21 ), shortness of breath (n = 18), and epistaxis (n = 17).3 In the total workforce of 257,71 were considered affected on the basis of at least 1 of the following criteria: respiratory symptoms not accounted for by another disease, abnormal chest radiograph, or lung biopsy. Imaging studies showed either widespread small nodular opacities or confluent patchy consolidation in 22 workers.1 Pulmonary function testing revealed findings consistent with a restrictive pattern, including reduction in total lung capacity and in diffusing capacity.

A similar disease occurred in an Algerian textile facility whose workers used the same painting process.4 In this outbreak, 6 employees out of a total of 12 developed disease, and 1 worker died. After 1 year, most patients in the Spanish cohort had significantly improved; a similar trend occurred after 5 years in 3 of the Algerian patients.2,5

Workers have used this painting technique since the early 1950s without recognized adverse health effects. The paint itself consisted of a 3-component substance that workers mixed with water and applied as a paste using a brush or sponge. Material safety data sheets indicated that all components were nonirritating polymers with low oral and dermal toxicity.6 However, in both the Spanish and Algerian factories, workers substituted white spirits for water as the carrier and applied the paint as an aerosolized spray.1 Furthermore, working conditions were described as poor in both outbreaks, and some exposed employees became symptomatic within I month of exposure.

Table 1.-Summary of 4 Rare Occupational Lung Diseases

After the outbreaks, Oottens et al7 conducted intratracheal investigations of all components of the painting system in hamsters and found that LD50 (ie, the lethal dose required to kill half of test subjects) was 10 to 1,250 times more toxic by this route of administration. However, for 2 of the components (Acramin FWR and Acramin FWN), the researchers observed no appreciable difference in toxicity by this route. Therefore, the precise cause of Ardystil syndrome remains unknown. In vitro studies in human cells have shown that toxicity is greatest in polycationic paint components.8 This cytotoxicity is greatly reduced when cells are co-incubated with polyanions.9

Ardystil syndrome presents several important and interrelated lessons. First, this outbreak is yet another demonstration of the limitations of animal studies in predicting toxicology in humans. In this case, substances that were believed to be nonirritating through a mucocutaneous exposure route were found to be profoundly irritating to the lung. second, reformulations and changes in practices may always present new risks of diseases arising in established work settings in ways that may not be easily predicted. Last, our understanding of the mechanisms of pulmonary toxicity remains limited. As one group of authors summarized, “The subacute time course, the unusual presentation, and the extreme severity of the disease are puzzling, particularly because these polymers would not be expected, from a toxicological viewpoint, to cause such spectacular pulmonary damage, even when inhaled as aerosols.”8lp209)

LIPOID PNEUMONIA

Lipoid pneumonia may result from either endogenous or exogenous causes. The most common exogenous causes include aspiration of fatty foods, oils, or petroleum medicinal preparations, frequently by debilitated patients. In a retrospective, nationwide study of 44 cases of lipoid pneumonia in France, Gondouin et al10 found that 4 cases had an occupational basis. The authors described the occupational exposure as “chronic inhalation of cutting mist or oily vapour either in a metallurgy plant (three cases) or a cable factory (one case).”10

Table 2,-Occupational Causes of Lipoid Pneumonia

Lipoid pneumonia has been documented in diverse occupational settings. Based on early pathologic studies, animal oils are believed to be the most powerful causes of lipoid pneumonia, followed by vegetable and mineral oils12 (see Table 2). However, the method of diagnosis is disputed. Some authorities state that bronchoalveolar lavage with transbronchial biopsy is sufficient; however, this technique has limitations both with respect to sensitivity and specificity, and an open biopsy may be required. The latter approach will also provide information about the extent of fibrosis.13

POPCORN WORKER’S LUNG

In 2000, an occupational medicine physician reported 8 former workers of a microwave popcorn factory with fixed obstructive lung disease to public health authorities in Missouri (USA).23 Four of these patients had sufficiently severe disease to warrant consideration for lung transplantation. The respiratory illness resembled bronchiolitis obliterans, with symptoms of cough and dyspnea on exertion, and spirometric findings showing obstruction without a bronchodilator response. In 2 of 3 cases for which tissue samples were available from open-lung biopsy, findings were consistent with bronchiolitis obliterans.24 Four of the patients had worked in a room where microwave popcorn flavoring agents were mixed, and 4 had worked only in microwave-popcorn packaging areas,25 A cross-sectional survey of current employees revealed a more widespread excess of respiratory morbidity: a 2.6-fold increase in workers’ symptoms of chronic cough and shortness of breath and a 3.3- fold increase in airway obstruction.24 Among never smoking workers, researchers observed a 10.8-fold increase in respiratory symptoms. At follow-up, most patients appeared to have an irreverisible yet stable pattern of fixed obstruction of the lung with partial improvement in symtpoms.23

Researchers singled out diacetyl, a butter-flavored ketone, as the likely cause of disease, given that high levels of the substance were found in the mixing room and that researchers observed a strong correlation between worker exposure to the substance and severity and frequency of airway obstruction. Findings from subsequent toxicity studies in rats have supported this association.26 Additional case reports are consistent with this hypothesis. For example, at another microwave popcorn packaging plant, a worker exposed to butter flavorings supplied by a different manufacturer developed fixed-airway obstruction.27 Researchers28″30 have also reported bronchiolitis obliterans in workers in other food manufacturing and flavouring industries.

Symptoms of Popcorn Worker’s Lung can extend beyond the lung to include eye, nose, and skin irritation, which may act as warning symptoms.23 Protective measures include installing isolated ventilation systems for flavor-mixing areas of food manufacturing facilities and requiring workers exposed to flavorings to wear air- purifying and paniculate respirators with organic vapor cartridges.24 FLOCK WORKER’S LUNG

Flock consists of short fibers cut from thin continuous strands (called tow) by means of rotary or guillotine cutters. Nylon and rayon are most frequently used to make flock, although other synthetic and natural fibers are used in certain applications. A variety of substances-such as titanium dioxide, ammonium ether, potato starch, tannic acid, and fatty alcohol derivatives-may be applied to the tow prior to cutting. After cutting, the flock is dried, screened, and bagged. Ultimately, flock fibers are applied to an adhesivecoated surface using an electrostatic process to produce a velvet-like coating. This application may be used to coat an object, such as a toy, or as a backing to generate upholstery material. Flock without adhesion is also used as a filler material; first, heating cures the adhesive, and the flocked product may then be subjected to finishing, embossing, and printing. Demand for flocked fabric has increased in recent years. In the United States, an estimated 2,500 workers are employed at 12 flock manufacturing companies, with an additional 100 companies applying flock.31

Pimentel et al32 reported the first documented outbreak of lung disease associated with exposure to nylon fibers in 1975 in 7 patients who developed a variety of lung diseases and 2 of whom had biopsy-proven interstitial lung fibrosis. The investigators also reproduced an impressive inflammatory response in guinea pigs exposed to nylon dust. However, these findings went largely unnoticed.

Between 1990 and 1991, 5 cases of interstitial lung disease were diagnosed among 88 workers in a plant manufacturing nylon flock upholstery in Ontario, Canada.13 Biopsies from the first 3 cases revealed desquamative interstitial pneumonias with diffuse alveolar damage. The investigators, unable to identify a chemical exposure with known pulmonary toxicity in the workplace, suspected that the cause was aflatoxin produced by mold growing on the surface of barrels of adhesive.

When 2 additional cases of interstitial lung disease were diagnosed at another plant owned by the same company in Rhode Island (USA), the employer requested an investigation by a local university in conjunction with the National Institute for Occupational Safety and Health (NIOSH). The investigators identified 7 cases of “flock worker’s lung” in a cohort of 165 current or former workers at the Rhode Island facility on the basis of findings either at biopsy or of bronchoalveolar lavage together with a restrictive lung defect and high-resolution computed tomography showing micronodularity or diffuse ground-glass appearance.34

The median time of onset from time of hire to symptoms (dyspnea and progressive dry cough) was 6 years (range = 9 months-31 years). At the time, the researchers reported pathological findings as nonspecific interstitial pneumonia in 5 patients and bronchiolitis obliterons organizing pneumonia in I patient. Although environmental investigations failed to identify the specific cause, researchers began to doubt the role of a microbial-related agent. First, 2 additional cases of interstitial lung disease had developed in the Canadian plant in spite of remediation measures for mold. second, air sampling at the Rhode Island facility showed only modest concentrations of fungal spores and endoloxin. However, these investigators did find high levels of dust overall, and high levels of respirable nylon fragments specifically.33 Subsequent animal studies demonstrated that respirable nylon flock fragments, even without a finish, could provoke an impressive acute inflammatory response.35 Eventually, a total of 8 cases were reported at the Rhode Island plant.31 All improved after leaving work at the facility.

At a workshop hosted by NIOSH in which attendees reviewed lung biopsy material from 15 available cases (including a revaluation of the Canadian cases), a consensus was reached that the characteristic lesion for this dis ease was, “a lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia represented by lympho
id aggregates.”^sup 36(p2005)^ Therefore, we regard Flock Worker’s Lung as a new occupational lung disease.

Bear in mind that initial criteria for a diagnosis of Flock Worker’s Lung were relatively stringent, as is appropriate for research purposes. However, when more liberal criteria were applied, more potentially affected workers were identified. In a group of 32 symptomatic flock workers who did not fulfill previously established criteria, high-resolution computed tomography revealed that 19 exhibited groundglass or micronodular patterns.37 Because flock fragments cut from tow are large, what remained to be explained was the origin of the respirable nylon dust. Eventually, researchers discovered that workers frequently cut tow incompletely, leaving a frayed end. This frayed end can subsequently break off, generating respirable fragments.38

References

1. Brown CD, Hewan-Lowe K, Kseibi SA, Huang YY. Exogenous lipoid pneumonia secondary to an occupational exposure in a furniture factory (abstract]. Chest. 2004;126:997S.

2. Moya C, AnIo JM, Taylor AJ. Outbreak of organising pneumonia in textile printing sprayers. Lancet. 1994;344:498-502.

3. Sole A. Cordero PJ, Morales P, Martinez ME, Vera F, Moya C. Epidemic outbreak of interstitial lung disease in aerographics textile workers. The “Ardystil syndrome”: a first-year follow up. Thorax. 19%;51:94-95.

4. Ould Kadi F, Mohammed-Brahim B, Fyad A, Lellou S, Nemery B. Outbreak of pulmonary disease in textile dye sprayers in Algeria. Lancet. 1994; 344:962-963.

5. Ould Kadi F, Abdesslam T, Nemery B. Five-year follow-up of Algerian victims of the “Ardystil syndrome.” Ear Respir J. 1999; 13:940-941.

6. Camus P, Nemery B. A novel cause for bronchiolitis obliterans organizing pneumonia: exposure to paint aerosols in textile workshops. Ear Respir J. 1998; [1:259-262.

7. 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. 1997:54:376-387.

8. Hoet PH, Gilissen LP, Leyva M, Nemery B. In vitro cytotoxicity of textile paint components linked to the “Ardystil syndrome.” Toxicol Sci. 1999;52:209-216.

9. Hoet PH, Gilissen LP, Leyva M, Nemery B. Polyanions protect against the in vitro pulmonary toxicity of polycationic paint components associated with the Ardystil syndrome. Toxicol Appl Pharmacol. 2001:175:184-190.

10. Gondouin A, Manzoni P, Ranfaing E, et al. Exogenous lipid pneumonia: a retrospective multicentre study of 44 cases in France. Ear Respir J. 1996;9:1463-1469.

11. National Institute of Occupational and Safety and Health. National Occupational Exposare Survey (1981-1983). http://www.cdc. gov/noes. Accessed May 12, 2008.

12. Pinkerton H. The reaction to oils and fais in the lung. Arch Palhol. 1928;5:380-401.

13. Pujol JL, Barneon G, Bousquet J, Michel FB. Godard P. Interstitial pulmonary disease induced by occupational exposure to paraffin. Chest. 1990:97:234-236.

14. Oldenburger D, Maurer WJ, Beltaos E, Magnin GE. Inhalation lipoid pneumonia from burning fats. A newly recognized industrial hazard. JAMA. 1972:222:1288-1289. 15. Carby M, Smith SR. A hazard of paint spraying. Lancet. 2000:355:896.

16. Kizer KW, Golden JA. Lipoid pneumonitis in a commercial abalone diver. Undersea Biomcd Res. 1987:14:545-552.

17. Yokohori N, Homma S, Tanaka S, et al. Exogenous lipoid pneumonia induced by inhalation of insecticide [in Japanese]. Nihon Kokyuki Gakkai Zasshi. E999;37:583-588.

18. Perol M, Vallon C, Vallon JJ, Guerin JC. Lipid pneumopathy caused by occupational exposure to cutting oil. Rev Mal Respir. 1989:6:271-274.

19. Beermann B, Christensson T. Moller P, Stillstrorti A. Lipoid pneumonia: an occupational hazard of fire eaters. Br Med J (Clin Res Ed). 1984:289:1728-1729.

20. Cullen MR, Balmes JR. Robins JM, Smith GJ. Lipoid pneumonia caused by oil mist exposure from a steel-rolling tandem mill. Am J lnd Med. 1981;2:51-58.

21. Skorodin MS, Chandrasekhar AJ. An occupational cause of exogenous lipoid pneumonia. Arch Pathol Lab Med. 1983:107:610-611.

22. Weissman H. Lipoid pneumonia: report of two cases. Am Rev Tuberc. 1951:64:572-576.

23. Simoes E, Maley R, Kreiss K, Malone J, Kanwa! R. Fixed obstructive lung disease in workers at a microwave popcorn factory: Missouri, 2000-2002. MMWR. 2002:51:345-347.

24. Akpinar-Elci M, Travis WD, Lynch DA, Kreiss K. Bronchiolitis obliterans syndrome in popcorn production plant workers. Ear Rspir J. 2004:24:298-302.

25. Kreiss K, Gomaa A, Kullman G, Fedan K, Simoes EJ, Enright PL. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med. 2002:347:330-338.

26. Hubbs AF. Battelli LA, Goldsmith WT, et al. Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. To-iicol Appl Pharmacol. 2002; 185:128-135.

27. Parmet AJ, Von Essen S. Rapidly progressive, fixed airway obstructive disease in popcorn workers: a new occupational pulmonary illness? J Occup Environ Med. 2002;44:216-218.

28. Alleman T, Darcey DJ. case report: Bronchiolitis obliterans organizing pneumonia in a spice process technician. J Occup Environ Med. 2002:44:215-216.

29. National Institute for Occupational Safety and Health. Health Hazard Evaluation and Technical Assistance Report. International Bakers Services, Inc.. South Bend, Indiana. Washington, DC: Department of Health and Health Services; 1986. DHHS publication no. 85-171-1710.

30. Lockey J, McKay R, Barth E, Dahlsten J, Baughman R. Bronchiolitis obliterans in the food flavoring manufacturing industry [abstract). Am J Respir CHr Care Med. 2002; 165: A461. 31. Kern DG, Crausman RS, Durand KTH, Nayer A. Kuhn C 3rd. Flock worker’s lung: chronic interstitial lung disease in the nylon flocking industry. Ann Intern Med. 1998; 129:261-272 [erratum: 1999: 130:246],

32. Pimentel JC, Avila R, Lourenco AG. Respiratory disease caused by synthetic fibres: a new occupational disease. Thorax. 1975;30: 204-219.

33. Lougheed MD, Roos JO, Waddell WR, Munt PW. Desquamative interstitial pneumonitis and diffuse alveolar damage in textile workers. Potential role of mycotoxins. Chest. 1995;108:1196-2000.

34. Kem DG, Durand KTH, Crausman RS, et al. Chronic interstitial lung disease in nylon flocking industry workers: Rhode Island, 1992- 1996. JWWWA Morh Mortal WkIy Rep. 1997:46:897-901.

35. Porter DW, Castranova V, Robinson VA, et al. Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant. J Toxicol Environ Health A. !999:57: 25-45.

36. Eschenbacher WL, Kreiss K. Lougheed MD, Pransky GS, Day B, Castellan RM. Nylon flock-associated interstitial lung disease. Am J Respir Crit Care Med. 1999;159:2003-2008.

37. Weiland DA, Lynch DA, Jensen SP, et al. Thin-section CT findings in flock worker’s lung, a work-related interstitial lung disease. Radiologv. 2003:227:222-231.

38. Burkhart J. Piacitelli C, Schwegler-Berry D, Jones W. Environmental study of nylon flocking process. J Toxicol Environ Health Part A. 1999:57:1-23.

M. Sarper Erdogan, MD, PhD; Christopher J. Martin, MD, MSc

M. Sarper Erdogan is with Istanbul University in Turkey. Christopher J. Martin is with West Virginia University in Morgantown.

For comments and further information, address correspondence to Dr Christopher J. Martin, Institute of Occupational and Environmental Health, Department of Community Medicine, West Virginia University School of Medicine. PO Box 9091. Morgantown, WV 26506-9190, USA. E-mail: [email protected]

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