Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) and desquama- tive interstitial pneumonia (DIP) are viewed as a continuum of smoking-induced diseases. Another smoking-related condition, respiratory bronchiolitis (RB), is usually found in asymptomatic smokers and a few ex-smokers. It is unclear whether it is a disease entity or a normal response to smoking.
Characteristic histopathological finding in RB-ILD is the accumulation of alveolar macrophages within respiratory bronchioles and surrounding alveoli. Macrophages contain light-brown, finely granular pigmentation due to accumulation of smoke con- stituents. Chronic inflammation of neighboring bronchiolar and alveolar walls is present (Figure 7.1).
Typical histopathological features of DIP are diffuse alveolar septal thickening, hyper- plasia of type II pneumocytes, and intensive accumulation of macrophages within the alveoli. The distribution of macrophages tends to be diffuse rather than bronchiolocen- tric as seen in RB-ILD (Figure 7.2).
Clinical features of RB-ILD and DIP are quite similar. Slowly progressive exertional dyspnea and nonproductive cough are frequents symptoms. Chest pain is rare, and finger clubbing is seen in 25% of the patients. End-inspiratory fine crackles over the lung bases may occur. In most cases, these diseases are benign; occasionally, extensive fibrosis supervenes.
These entities are strongly associated with cigarette smoking, except for a few sporadic cases of DIP in nonsmokers. The antiprotease-protease and antioxidant-oxidant imbal- ance plays a role in ILD. Lung fibroblasts release neutrophil and monocyte chemotactic factors in response to smoke. The lung fibroblasts modulate the inflammatory cell recruitment into the lung. Additionally, epithelial and endothelial cells contribute to the enhancement of inflammatory lung injury.
Diagnostic procedure includes lung function testing, chest radiological analysis, and bronchscopy with the lung lavage procedure. Lung function test often shows restrictive or mixed restrictive and obstructive pattern of pulmonary impairment. The most common pulmonary function abnormality, however, is reduced carbon monoxide (DLCO) diffusing capacity. Severe functional impairment, especially reduced DLCO, is attributable to coexistent emphysema. In patients with DIP, only restrictive pattern is detected with reduced DLCO. Severe hypoxemia is observed in advanced disease.
In RB-ILD patients, chest radiographs show parenchymal, centrilobular, ill-defined micronodules with or without ground-glass opacities (Figure 7.3a, b). Bilateral, sym- metric, and predominantly basal and peripheral ground-glass attenuation is a HRCT feature of DIP, although irregular linear opacities and cystic spaces are also observed.
(Figure 7.4a, b).
Bronchoalveolar lavage cell analysis in RB-ILD reveals a preponderance of brown- pigmented macrophages with a mild neutrophil increase (Figure 7.5). On the other hand, in DIP there is an increase in lymphocytes, neutrophils, and occasionally eosinophils.
Transbronchial lung biopsy is not useful in diagnosing these diseases.
7
Respiratory Bronchiolitis Associated Interstitial Lung Disease and
Desquamative Interstitial Pneumonia
47
In a smoker, the combination of typical HRCT finding, pulmonary function tests, and lung lavage analysis may allow the diagnosis of these diseases made without open lung biopsy. If there is any doubt, then an open lung biopsy should be performed (Table 7.1).
Smoking cessation induces spontaneous regression of these diseases. Thus, the temp- tation to start drug therapy should be resisted. Corticosteroid therapy induces modest clinical benefit in DIP but not in RB-ILD.
48 Clinical Atlas of Interstitial Lung Disease
Figure 7.1. Respiratory bronchiolitis associated interstitial lung disease (RB-ILD).
Respiratory bronchioli and adjacent alveoli are filled by macrophages containing fine granular brown pigment.
Figure 7.2. Desquamative interstitial pneumonia (DIP). Alveolar spaces are filled with macrophages containing fine granular brown pigment in cytoplasm. Alveolar septa with mild fibrosis.
Figure 7.3. Chest x-ray of a lady who smoked heavily for many years shows diffuse, sharpened reticular pattern (a). CT scan of the same patient shows small vague nodules and septal thickening (b). Lung lavage analyses revealed numerous brown pigmented macrophages. The final diagnosis was respiratory bronchiolitis associated lung disease and the patient was advised to quite smoking.
RB-ILD and DIP 49
Table 7.1. Differences between respiratory bronchiolitis associated interstitial lung disease (RB-ILD) and desquamative interstitial pneumonia (DIP).
Feature RB-ILD DIP
Severity of lung function impairment + ++
Histopathological finding
Pigmented macrophages + ++
within airspaces
Histological bronchocentricity ++ −
BAL Pigmented macrophages Pigmented macrophages, neutrophils, and eosinophils HRCT
Ground glass + ++
Alveolar septal thickening Peribronchial Diffuse
Micronodi ++ −
Honeycombing − −
Therapy Smoking cessation alone Smoking cessation and corticosteroids
Figure 7.4. Plain radiograph of the chest shows ground-glass opacities, distributed predominantly in the lower lobes in a patient with DIP (a). HRCT scan of the same patient shows the peripheral distribution of ground-glass opacities with no fibrotic changes (b).
Figure 7.5. Brown pigmented macrophage surrounded with alveolar macrophages. BAL fluid cytology, original magnification
×1000, MGG stain (May-Grünwald-Giemsa).
50 Clinical Atlas of Interstitial Lung Disease
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