Respiratory bronchiolitis associated with interstitial lung disease and desquamative interstitial pneumonia

This article highlights the smoking-related interstitial lung diseases including respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans cell histiocytosis (PLCH), combined pulmonary fibrosis and emphysema (CPFE) and smoking-related interstitial fibrosis (SRIF). All share cigarette smoking as a likely cause of presenting disease, of which characteristic clinical findings, radiologic features, and histopathology will be reviewed. For a majority of the smoking-related interstitial lung diseases, smoking cessation is a vital first step to reversing disease course or slowing progression, along with directed anti-inflammatory or immunosuppressant therapy.

Respiratory bronchiolitis-associated interstitial lung disease (ILD), desquamative interstitial pneumonia (DIP), and pulmonary Langerhans cell histiocytosis are entities of smoking-related ILD. While clinically regarded as 2 separate forms of idiopathic interstitial pneumonia, DIP, and respiratory bronchiolitis-associated ILD are thought to be representing ends of a continuous spectrum of disease that primarily affects tobacco smokers. This case report presents a 53-year-old female patient who has 58 pack-year smoking history who has been experiencing a dry cough and epigastric pains for 2 years. Open-lung biopsy is performed and histopathology indicated smoking-related interstitial fibrosis. The patient did not stop smoking, which after a year leads to significant clinical deterioration with a notable decrease in diffusion for carbon monoxide capacity. Upon smoking cessation and treatment with corticosteroids, a significant clinical improvement is achieved. In smokers complaining of cough and reduced exercise tolerance and in whom evidence of interstitial fibrosis is demonstrated radiologically, DIP should be considered as a differential diagnosis. Smoking is the exclusive etiologic factor of pathogenesis of DIP.

Cigarette smoking is the primary causative factor for lung carcinoma and respiratory bronchiolitis (RB), particularly RB-associated interstitial lung disease (RB-ILD). However, the link between lung cancer and RB/RB-ILD remains undefined. We examined whether pathological fibrosis lesions exist simultaneously in patients with lung carcinoma because the fibrous lesions could be precancerous.

Clinical, radiological, and pathological features were consecutively evaluated in 67 current smokers, 22 ex-smokers, and 35 nonsmokers who underwent surgical resection for lung carcinoma. The presence of interstitial changes was evaluated by high-resolution computed tomography (HRCT). The pathological examination focused on RB, RB with fibrosis, and coexistent interstitial changes.

RB with fibrosis was observed in 13/67 current smokers with centrilobular nodular and/or patchy ground-glass opacities patterns or emphysema on HRCT. RB without fibrosis was observed in 12/67 current smokers with a centrilobular pattern, emphysema, or a normal pattern on HRCT. The Brinkman smoking index was significantly higher in the RB with fibrosis group (1278±133) than in the RB without fibrosis group (791±131). No RB with/without fibrosis features were noted in nonsmokers or ex-smokers. Squamous cell carcinoma was observed in 11/13 patients with RB with fibrosis, whereas adenocarcinoma was observed in 7/12 patients with RB without fibrosis.

Squamous cell carcinoma located in peripheral areas was primarily observed in patients with RB with fibrosis, whereas adenocarcinoma was primarily observed in patients with RB without fibrosis. Interstitial fibrosis with RB caused by continuous heavy cigarette smoking may increase the risk of developing squamous cell carcinoma.

Bronchiolitis obliterans–organizing pneumonia (BOOP) is an inflammatory and fibrosing disease involving the distal bronchioles, bronchiolar ducts, and alveoli. We studied 91 patients with BOOP. Univariate analysis was used to relate age, sex, smoking, morphology, and expression of immunohistochemical markers CD68, D2-40, CD31, CD34, collagen IV, collagen III, platelet-derived growth factor receptor, and vascular endothelial growth factor (VEGF) with the response to corticosteroid therapy. Seventy-two patients had idiopathic BOOP and 19 secondary BOOP. The median age of the patients was 59.54 years. Most patients were current or former smokers. All cases had a patchy lesion consisting of small buds of fibromyxoid tissue in small bronchioles, bronchiolar ducts, and alveoli. The buds contained collagen and reticulin fibers, fibroblasts, macrophages, mononuclear inflammatory cells, and vessels in different proportions. We found no morphologic differences between primary and secondary BOOP. Patients younger than 38 years and nonsmokers had a significant good response to corticosteroid therapy. Favorable morphologic predictors were the presence of large bronchial plugs and mild inflammatory reaction (P = .093). By immunohistochemistry, the presence of collagen IV with the absence of collagen III, CD68-positive cells and positive VEGF were associated with a good response to corticosteroid therapy. We conclude that age, smoking, localization, and extension of proliferative intrabronchiolar plugs and positive immunostains for CD68, VEGF, and collagen IV with negative collagen III were useful to predict response to corticosteroid therapy and relapse.