Key characteristics of smoking related ILDs

Transcription

1 Combined pulmonary fibrosis and emphysema (CPFE) syndrome, desquamative interstitial pneumonia (DIP), and respiratory bronchiolitis with interstitial lung disease (RB-ILD) Vincent Cottin National Reference Center for rare pulmonary diseases University of Lyon 28 Avenue du Doyen Lepine Lyon France AIMS To know the spectrum of smoking-related interstitial lung diseases (ILDs). To be able to diagnose and manage RB-ILD and DIP. To be able to recognise pulmonary langerhans cell histiocytosis. To understand the main characterstitics and consequences on management of the syndrome of CPFE. SUMMARY The smoking-related interstitial lung diseases (ILDs) comprise several diseases that share a strong causal relationship with tobacco smoking, and may coexist and/or be associated with emphysema. They include the traditional smoking-related ILDs (respiratorybronchiolitis associated ILD, RB-ILD; desquamative interstitial pneumonia, DIP; and pulmonary Langerhans cell histiocytosis) and the syndrome of combined pulmonary fibrosis and emphysema (CPFE), more recently individualized. Some authors also include in this group entities that are linked to tobacco smoking but can occur in a different etiological context such as acute eosinophilic pneumonia (box 1) [1], or rheumatoid arthritisassociated ILD.

2 Key characteristics of smoking related ILDs The key characteristics of chronic smoking related diffuse lung disease are listed in table 1 [1] and on the following page [2].

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4 The syndrome of combined pulmonary fibrosis and emphysema There is an increasing awareness of comorbid conditions frequently associated with idiopathic pulmonary fibrosis (IPF), including emphysema, cardiovascular disease, thromboembolic disease, and obstructive sleep apnoea. Recent retrospective data suggest that 21 to 33% of patients with IPF may have coexisting emphysema. The association of emphysema to IPF has been coined the combined pulmonary fibrosis and emphysema (CPFE) syndrome to account for characteristic clinical, functional, imaging, and outcome features. Characteristics of patients with the CPFE syndrome include male predominance, tobacco smoking, severe dyspnea, subnormal spirometry findings, severely impaired transfer capacity for carbon monoxide, hypoxemia at exercise, high frequency of paraseptal emphysema, and a high probability (30-50%) of severe pulmonary hypertension impacting prognosis. CPFE is a syndrome with characteristic presentation, including very low diffusion capacity contrasting with subnormal spirometry, occurring in heavy smokers with severe dyspnea and exercise limitation. It may be overlooked because of subnormal lung volumes, however gas exchanges are severely altered. Despite moderate or severe emphysema, a large proportion of patients with CPFE have FEV1/FVC > 70% indicating that GOLD criteria for chronic obstructive lung disease may not be applicable. In addition, diagnostic criteria of IPF may not apply, owing to difficulties to ascertain honeycomb changes in patients with associated emphysema UIP and a high frequency of mild to moderate ground glass opacities. The CPFE syndrome may occur in the context of connective tissue disease especially rheumatoid arthritis. A limited amount of data is available regarding lung pathology in patients with CPFE. Indeed, severe alteration of gas exchange and emphysema features at imaging may explain that lung biopsy is rarely performed, as in the present case. A variety of pathology patterns of pulmonary fibrosis has been reported in patients with CPFE, including predominantly UIP pattern, however nonspecific interstitial pneumonia, desquamative interstitial pneumonia (with extensive fibrosis), respiratory bronchiolitis associated interstitial lung disease, airspace enlargement with fibrosis, or unclassifiable smokingrelated interstitial fibrosis may be observed. The natural course of disease in CPFE may encompass episodes of acute exacerbation of pulmonary fibrosis, a complication seldom reported previously in CPFE. The presence of significant emphysema impacts FVC measurement, and thus changes in FVC alone may not be a reliable indicator of disease. Patients with CPFE should be excluded from IPF clinical trials. In fact, a decline in FEV1 by 10% or more at 6 or 12 months may be useful in assessing progression of disease, contrasting with monitoring of lone IPF using serial changes in FVC and DLco. The main predictor of subsequent mortality is precapillary pulmonary hypertension that portends a dismal prognosis. Whether survival of patients with IPF is impacted by coexistent emphysema (e.g. CPFE) is controversial due to difficulties in controlling for severity. A composite physiologic index may account for disease severity. There are no recommendations for treatment of pulmonary fibrosis, emphysema or pulmonary hypertension in the setting of CPFE. It is unknown if treating these components of disease influences clinical outcomes. Patients with CPFE are likely to require long-term oxygen therapy. Isolated observations indicate that therapy specific for pulmonary hypertension may improve hemodynamics, but the potential clinical and survival benefit is unknown. Recent data have recommended against combination therapy with prednisone, azathioprine, and high-dose N-acetylcysteine in IPF, however corticosteroids may still have a role in selected patients with a pathologic pattern of nonspecific interstitial pneumonia. The potential benefit of anti-fibrotic drugs (pirfenidone, nintedanib) in patients with CPFE has not been specifically evaluated.

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7 EVALUATION 1. In the revised 2013 ATS/ERS classification of idiopathic interstitial pneumonias, which of the followings belong to the group of smoking-related interstitial lung diseases? a) Idiopathic nonspecific interstitial pneumonia (NSIP) b) Respiratory bronchiolitis-interstitial lung disease (RB-ILD) c) Desquamative interstitial pneumonia (DIP) d) Pulmonary Langerhans cell histiocytosis (PLCH) e) Combined pulmonary fibrosis and emphysema (CPFE) Answers B,C 2. In desquamative interstitial pneumonia (DIP), which of the followings are correct: a) 60-90% of patients are smokers b) Most patients are asymptomatic c) Typical HRCT findings are prominent centrilobular nodules and ground glass opacities d) Alveolar spaces are diffusely filled with pigment-laden macrophages e) Response to corticosteroids is usually good Answers : A,D 3. In patients with pulmonary Langerhans cell histiocytosis, which of the following treatments can be considered a) Smoking cessation b) Cladribine c) Macrolide therapy d) Pleurodesis in case of pneumothorax e) Lung transplantation Answers : A,B,D,E 4. In patients with the syndrome of combined pulmonary fibrosis and emphysema, which of the following are correct a) All patients are smokers or ex-smokers b) The syndrome may occur in patients with rheumatoid arthritis c) The main determinant of prognosis is precapillary pulmonary hypertension d) There is good evidence that patients should be treated similarly as those with idiopathic pulmonary fibrosis e) Genetic testing may contribute to the diagnosis. Answers : B,C