To the Editors:
Chronic obstructive pulmonary disease (COPD) is characterised by progressive and poorly reversible airflow obstruction due to small airway disease and emphysema. Cigarette smoking is the major cause of COPD, but the disease also occurs in nonsmokers. In nonsmokers, environmental factors (e.g. second-hand smoking and inhalation of toxic gas), genetic factors (e.g. the rare α1-antitrypsin deficiency) and infectious factors (e.g. HIV infection) have been implicated in the pathogenesis of the disease. We report on two cases of COPD with emphysema in nonsmokers with long-standing undiagnosed coeliac disease.
A 71-yr-old female was referred to our hospital (Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France) for dyspnoea and cough, which had evolved over 5 yrs. She had suffered from alternating diarrhoea and constipation for many years, ascribed to functional bowel disease. She had never been exposed to inhaled toxics and had never smoked. Examination revealed a body mass index (BMI) of 18 kg·m−2 and a chest computed tomography (CT) image revealed pulmonary distension and emphysema (fig. 1). Spirometry revealed severe airflow limitation (table 1). Serum α1-antitrypsin was normal. Treatment with long-acting bronchodilators was initiated. After 7 yrs of follow-up, the patient complained of progressive weight loss (BMI 15 kg·m−2) and increased diarrhoea. Vitamin D deficiency was found, suggesting malabsorption. Anti-endomysium, anti-gliadin and anti-transglutaminase antibodies were detected. Gastroscopy revealed a macroscopic aspect of pavimental mucosa and duodenal biopsies showed subtotal villous atrophy with increased numbers of intraepithelial lymphocytes, confirming coeliac disease. Diarrhoea and weight loss improved markedly on a gluten-free diet, but no significant changes in lung function were observed.
a) High-resolution computed tomography images obtained in patient 2 reveals focal areas of low attenuation (arrowheads) within a homogeneous background of lung parenchyma, characterising centrilobular emphysema. b) Bullous emphysema in the same patient.
A 59-yr-old female was referred to our hospital (Hôpital Cochin, Assistance Publique-Hôpitaux de Paris) after two episodes of acute bronchitis and weight loss of 5 kg. She had never smoked and had never been exposed to inhaled toxics. She also complained of asthenia, chronic pain of the wrists and fingers, and chronic itching for several years. She signalled that she had always had soft saddles. Examination showed mild malnutrition (BMI 18 kg·m−2). Laboratory tests showed chronic microcytic anaemia and severe iron deficiency. A chest CT image showed centrilobular and bullous emphysema, which predominated in lower lobes (fig. 1). Spirometry showed mild airflow limitation and plethysmography revealed pulmonary hyperinflation. Serum α1-antitrypsin was normal. The patient declined bronchoscopy and no bronchoalveolar lavage was performed. Gastroscopy was performed to explore iron deficiency and showed a typical pavimental aspect of duodenal mucosa. Biopsies revealed total villous atrophy with lymphocytic infiltrate of the mucosa. Antibodies against gliadin, endomysium and transglutaminase were all positive. Further exploration showed marked vitamin D deficiency and severe osteoporosis. Coeliac disease was treated with a gluten-free diet, which resulted in a rapid improvement in itching, joint pain and diarrhoea. No significant changes in pulmonary abnormalities occurred.
Coeliac disease was originally considered a rare malabsorption syndrome of childhood, but is now recognised as a common condition that may be diagnosed at any age. Coeliac disease may affect many organ systems including the neurological system, skin and liver 1. Previous reports have suggested links between coeliac disease and several pulmonary manifestations, including diffuse pulmonary nodules, interstitial fibrosis, lymphocytic bronchoalveolitis and pulmonary haemosiderosis 2.
An association between emphysema and coeliac disease has been previously suggested 3–5. In a study of a case of malabsorption, intestinal mucosal atrophy and ulceration, cirrhosis, and emphysema, the authors suggested that emphysema was unrelated to coeliac disease because the patient was a heavy smoker 3. In another report, coeliac disease was associated with emphysema, which was ascribed to α1-antitrypsin deficiency 5. In a pathological study of lung specimens obtained in 14 patients (10 current or ex-smokers) with coeliac disease complaining of respiratory symptoms (e.g. dyspnoea and/or cough), Edwards et al. 4 described airflow obstruction in seven patients and peribronchiolar fibrosis in 12 patients. However, because lung function was normal in the four nonsmokers and because most bronchiolar abnormalities were found in current or ex-smokers, the authors suggested that these findings were unrelated to coeliac disease 4.
Our cases differ from previous reports in that both patients were lifelong nonsmokers and had no α1-antitrypsin deficiency. Although we cannot rule out that the observed associations between coeliac disease and emphysema occurred by chance, our report is consistent with the findings of Tarlo et al. 6 who reported mild airflow obstruction in 18 subjects with biopsy-proven coeliac disease compared with 18 control subjects matched for age, sex and smoking.
Coeliac disease is a unique autoimmune disorder because the environmental precipitant (gluten) is known 1. Recently, evidence has emerged that auto-immunity may be involved in the pathogenesis of alveolar destruction characteristic of emphysema 7. Because autoimmune diseases are often associated, it is possible that both diseases coexist and/or that auto-antibodies share antigen specificity. Another possible explanation is related to long-standing malnutrition. Severe malnutrition caused by starvation during World War II or by anorexia nervosa has been associated with the development of emphysema 8. Furthermore, vitamin D deficiency, which was present in our patients, has been linked with abnormal lung function 9. We suggest that long-standing malabsorption occurring in patients with coeliac disease may induce lung inflammation and emphysema. In support of the latter hypothesis, Brightling et al. 2 reported CD4+ lymphocytic bronchoalveolitis in a 68-yr-old female with a 1-yr history of dry cough, which improved markedly after several months on a gluten-free diet. We could not demonstrate such findings in our patients because patient 1 had severe bronchial obstruction and patient 2 declined bronchoscopy.
In summary, we suggest that coeliac disease diagnosis should be considered in patients with emphysema, especially when classical risk factors for emphysema (e.g. smoking) are absent. Further research is also warranted to examine the prevalence of emphysema in patients with coeliac disease. If confirmed, the association between emphysema and coeliac disease may provide new insights into the pathogenesis of emphysema and coeliac disease.
Footnotes
Statement of Interest
None declared.
- ©ERS 2010
