Lung interstitial fibrosis

Shaver s disease A disease of the lungs found in workers exposed to fumes or dusts containing aluminium oxide. It is a type of pneumoconiosis and results in interstitial fibrosis and decreased lung function. 

Inhalation of monomethylhydrazine was not carcinogenic in rats or dogs, but mice exposed at 2 ppm for 1 y exhibited an increased incidence of lung tumors, nasal adenomas, nasal polyps, nasal osteomas, hemangioma, and liver adenomas and carcinomas. Hamsters exposed at 2 or 5 ppm exhibited an increased incidence in nasal polyps, interstitial fibrosis of the kidney, and benign adrenal adenomas. An increase in nasal adenomas was seen in hamsters exposed at 5 ppm. 

A number of studies of the toxicity of zinc oxide/hexachloroethane smoke have been conducted (Brown et al. 1990 Karlsson et al. 1986 Marrs et al. 1983). These studies demonstrate that smoke exposure results in pulmonary inflammation and irritation. When male Porton Wistar rats were exposed to hexachloroethane/zinc oxide smoke for 60 minutes, the lungs showed pulmonary edema, alveolitis, and areas of macrophage infiltration 3 days later. At 14 days, there was interstitial fibrosis and macrophage infiltration. At 28 days, increased fibrosis and macrophage infiltration were noted. However, these same symptoms occurred when the animals inhaled zinc chloride there was no apparent synergism between the zinc chloride and residual hexachloroethane (Brown et al. 1990 Richard et al. 1989). This is consistent with the fact that smoke contains little hexachloroethane and the observation that acute exposure to 260 ppm hexachloroethane had no effects on the lungs of rats (Weeks et al. 1979). 

A greater degree of inflammation can lead to permanent lung damage or death. The respiratory bronchioles become obliterated (bronchiolitis obliterans), the alveoli are filled with proteinaceous edema fluid (heavy, wet lungs), and the inflammatory process can turn into interstitial fibrosis. 

As discussed in Section 3.2 and Chapter 2, numerous studies of occupationally-exposed adult workers identify respiratory effects including interstitial fibrosis, lung cancer, and pleural and/or peritoneal mesotheliomas, as critical health effects, of concern from exposure to airborne asbestos. T ically, these health effects follow chronic exposures and exhibit latencies of 10-40 years, although some cases of asbestosis and pleural plaques have been reported following subchronic exposure. 

Katjalainen A, Anttila S, Heikkila L. 1993b. Ix)be of origin of lung cancer among asbestos-exposed patients with or without diffuse interstitial fibrosis. Scand J Work Environ Health 19(4) 102-107. 

Interstitial A term used as an adjective relating to spaces within a tissue or organ. Pulmonary interstitial fibrosis refers to fibrosis (scarring) occurring within lung tissue. 

Parenchyma The functional cells or tissue of a gland or organ for example, the lung parenchyma. The major lung parenchymal abnormality associated with exposure to asbestos is the development of scar-like tissue referred to as pulmonary interstitial fibrosis or asbestosis. 

Pulmonary interstitial fibrosis Scar-like tissue that develops in the lung parenchymal tissue in response to inhalation of dusts of certain types of substances such as asbestos. 

Pulmonary interstitial fibrosis associated with deposition of collagen, progressive lung stiffening and impaired gas exchange, disability, and death occurred in many asbestos workers. 

In patients with definite or probable methotrexate-induced lung injury, the predominant clinical features include shortness of breath, cough, and fever (13). Pathological examination usually shows an interstitial inflammatory cell infiltrate (sometimes granulomatous or with alveolar damage), and variable degrees of interstitial fibrosis. Unfortunately, confirmatory evidence is sometimes hard to obtain, particularly in patients with rheumatoid arthritis in whom rheumatoid interstitial lung disease can also occur. Infectious pneumonias, particularly viral or Pneumocystis jiroveci pneumonia, which resemble methotrexate pneumonitis and can occur as a result of immunosuppression, should also be carefully excluded. 

Interstitial pneumonitis with severe respiratory failure has been reported in two patients (SEDA-21, 389) (SEDA-22, 418). One patient improved after mycophenolate mofetil was withdrawn, but interstitial fibrosis was found on serial lung biopsies. The other patient died from respiratory failure 3 months later. Although other drugs may have been involved in these two patients, one other reported case with recurrence of respiratory failure on each rechallenge of mycophenolate is particularly convincing. 

The manufacturers have on record in the USA several pulmonary adverse effects during isotretinoin therapy, including worsening of asthma (SEDA-21,162), recurrent pneumothorax, pleural effusion, interstitial fibrosis, pulmonary granuloma, and deterioration in lung function tests. Exercise-induced asthma (35) may be caused by a significant reduction in the forced expiratory flow rate (36) and a drying effect of isotretinoin on the mucous membranes of the respiratory tract (37). 

---