A 48 year old woman presented with a history of fatigue, regular sputum production, and wheeze. High resolution computed tomographic scanning of the thorax demonstrated widespread bronchiectasis. Coeliac disease was diagnosed on the basis of an iron deficiency anaemia, subtotal villous atrophy on small bowel biopsy, and raised anti-gliadin and anti-endomysial antibodies. The temporal relationship of her bronchiectasis and coeliac disease, and the subsequent stabilisation of her clinical symptoms and improvement in pulmonary physiology following treatment with inhaled corticosteroids, suggests a relationship between the two conditions which may be due to immunological mechanisms.
- coeliac disease
- anti-neutrophil cytoplasmic antibody
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A 48 year old woman presented with a history of fatigue, episodes of winter bronchitis over six years, and daily sputum production and intermittent wheeze for 18 months. There was no history of pneumonia, whooping cough, measles, or tuberculosis and she had never smoked. As a child she had episodes of wheezy bronchitis which had resolved while a teenager. Examination revealed conjunctival pallor, no finger clubbing, and bilateral basal expiratory wheezes and coarse crackles. Pulmonary function showed a mixed restrictive and obstructive defect; forced expiratory volume in one second (FEV1) 1.68 l (predicted 2.7 l), forced vital capacity (FVC) 2.41 l (predicted 3.19 l), total lung capacity (TLC) 4.43 l (predicted 5.11 l), residual volume (RV) 1.31 l (predicted 1.77 l), peak expiratory flow rate (PEFR) 180 l/min. Gas transfer factor (Kco) was mildly reduced at 1.28 (predicted 1.64) and arterial oxygen saturation was 98%. Sputum samples grew Pseudomonas aeruginosa. A chest radiograph showed features suggesting bronchial wall thickening in the lower lobes, and high resolution computed tomographic scans (fig 1i and ii) demonstrated widespread cylindrical bronchiectasis affecting the middle lobe, lingula, and both lower lobes. The bronchiectasis was most severe in the basal segments of the lower lobes where there was also marked bronchial wall thickening and mucus plugging. Adjacent to several of the bronchi were areas of low attenuation suggestive of air trapping secondary to an associated obliterative bronchiolitis. Laboratory investigations failed to reveal a cause for her bronchiectasis; she had an increased polyclonal total IgG at 14.4 g/l (normal range (NR) 6–13), raised IgG3 at >1200 mg/l (NR 320–1160), and normal IgA and IgM. Antinuclear factor, rheumatoid latex, and avian and aspergillus precipitins were all negative. Alpha1-antitrypsin phenotype was MS. Sweat sodium levels were normal at 30 mmol/l and screening for the eight most common cystic fibrosis mutations found in our region was negative. Titres of antineutrophil cytoplasmic antibody (c-ANCA) directed against a recently characterised antigen bactericidal/permeability increasing protein (BPI) were raised at 74% (NR <17%) but were negative for proteinase 3.
She was also found to have a mild iron deficiency anaemia (haemoglobin 9.9 g/dl, mean corpuscular volume 71.5 fl, and ferritin 3 μg/l), a blood film showed evidence of microcytosis and hypochromia, and there were no features to suggest splenic atrophy. A duodenal biopsy specimen showed features of subtotal villous atrophy consistent with a diagnosis of coeliac disease which was supported by the finding of positive IgA anti-endomysial and raised anti-gliadin antibodies (IgG 106 U/ml, IgA 89 U/ml; NR 0–16 and 0–43, respectively).
Over the past two years she has been on and off a gluten free diet owing to poor tolerance. Her clinical symptoms have stabilised on treatment with inhaled beclomethasone and salbutamol and her lung volumes have all improved: FEV1 1.98 l, FVC 2.96 l, TLC 4.92 l, and RV 1.75 l.
Previous reports have suggested an association of coeliac disease with fibrosing alveolitis, bird fancier’s lung, farmer’s lung, sarcoidosis, idiopathic pulmonary haemosiderosis, lung abscess, and asthma,1 but this is the first reported association with bronchiectasis. “Partial fibrous obliteration of small airways and dilatation of larger airways” has been described following a necropsy from a single patient with coeliac disease and dyspnoea, though this patient had a purely restrictive physiological defect and did not have clinical or radiological features of bronchiectasis as in our case.2 Changes of chronic bronchitis have been reported in the open lung biopsy specimen from another patient with diffuse pulmonary disease and pleural thickening but it was not recorded whether or not the patient was a smoker.3
The wide range of pulmonary conditions reported in association with coeliac disease is analogous to ulcerative colitis, in which steroid sensitive bronchial inflammation and bronchiectasis are recognised complications.4 The cause of the association of pulmonary disorders with coeliac disease remains poorly defined. Absorption of an extrinsic allergen or immune complexes through an abnormal gastrointestinal mucosa may lead to the pulmonary disease.5 Alternatively, the association of coeliac disease with HLA status and various autoimmune diseases6suggests that a common disturbance in immunity may underlie both coeliac disease and pulmonary disorders. Our patient did not have either splenic atrophy or selective IgA deficiency7 which are associated with coeliac disease and which could predispose to development of recurrent infections and bronchiectasis. Interestingly, she had a positive ANCA recognising bactericidal/permeability increasing protein. This is found in the azurophilic granules of neutrophils and functions as an important inhibitor of lipopolysaccharide and endotoxin. It has recently been reported in association with both chronic inflammatory bowel disease8and cystic fibrosis.9 Its significance in our patient is uncertain but may be related to her bronchial infection withPseudomonas aeruginosa.10
Previous reports of pulmonary disease complicating coeliac disease, the close temporal relationship of the onset of symptoms from her bronchiectasis and coeliac disease, the stabilisation of her symptoms and the improvement in her pulmonary function tests with inhaled corticosteroids, and the absence of alternative factors to account for her bronchial disease all make it likely that her bronchiectasis is related to her coeliac disease.
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