Pulmonary involvement in primary Sjögren's syndrome

The aim of this thesis was to investigate pulmonary involvement in patients with primary Sjögren’s syndrome (pSS), in terms of pulmonary function and chronic obstuctive pulmonary disease (COPD) prevalence and its development over time in association with radiographic findings, pSS disease features and respiratory symptoms, taking cigarette smoking into account, as well as to study inflammatory markers in the airways of never-smoking patients with pSS compared to never-smoking controls. In study I, 51 consecutive SS patients were assessed by pulmonary function tests (PFTs) and the results were compared to population-based controls, taking cigarette smoking into account. pSS patients were also assessed by computed tomography (CT) of the chest and for pSS disease activity, respiratory symptoms, cigarette consumption as well as laboratory inflammatory and serological pSS features. COPD was a common finding in pSS patients, even among never-smoking patients. An obstructive pattern was the predominant PFT finding in pSS patients, although a superimposed restrictive lung disease could not be excluded. In study II, 37 pSS patients and 74 population-based matched controls were assessed using the forced oscillation technique (FOT). pSS patients showed FOT signs of obstruction affecting both the peripheral and central airways. Also, pSS patients with no spirometrical signs of obstructive airway disease and never-smoking pSS patients showed clear FOT signs of airway obstruction. Thus, FOT appears to be a sensitive method of detecting airway obstruction in pSS patients. In study III, induced sputum cytokines and leukocytes were assessed in 20 never-smoking patients with pSS and in 19 never-smoking population-based matched controls. Pulmonary function, disease activity, respiratory symptoms, as well as inflammatory and serological pSS features were assessed in the pSS patients. B-cell activating factor (BAFF), interleukin (IL)-6 and IL-8 were significantly increased in the induced sputum of pSS patients compared to populationbased controls, suggesting a specific ongoing inflammatory disease process in the airways of pSS patients. Cytokine levels in induced sputum were not associated with PFTs, disease activity, respiratory symptoms or serological features of pSS. In study IV, 40 patients with pSS, who previously participated in study I, were re-assessed by PFTs and for pSS disease activity, respiratory symptoms, cigarette consumption, as well as laboratory inflammatory and serological pSS features and high-resolution CT after a mean follow-up time of six years. Signs of both airway and pulmonary parenchymal involvment were commonly found with a co-existence of both an obstructive and a restrictive pulmonary function pattern, in which the latter tended to deteriorate over time. COPD remained a common finding, even in neversmoking pSS patients. Radiographic signs of bronchial involvement and interstitial lung disease were common. This thesis demonstrated that signs of airway and pulmonary parenchymal involvement are common in patients with pSS and may therefore be underdiagnosed. COPD being common, even in never-smoking pSS patients, suggests that the disease per se is involved in COPD development. Special attention and liberal assessment of pulmonary involvement in pSS patients is mandated.