Idiopathic interstitial lung disease with anti-SSA antibody.

OBJECTIVES: Consensus is lacking on the immunological tests to perform for diagnosis of interstitial lung diseases (ILDs). In particular, the value of detecting anti-SSA antibody in this context is unknown. We aimed to determine whether the detection of anti-SSA antibody in patients with ILD can identify a subgroup of patients with CTD. METHODS: We compared the characteristics of patients with newly diagnosed apparently idiopathic ILD with anti-SSA antibody [anti-SSA(+) group] and without anti-SSA antibody (control group). RESULTS; Anti-SSA(+) patients (n = 15) more often had extra-respiratory signs (xerostomia and ocular dryness), auto-immune features, a CT scan pattern of non-specific interstitial pneumonia and more severe lung function alteration than controls (n = 30). Of patients who were anti-SSA(+), 2 met the criteria for SS and 13 (86%) of 15 met the criteria for the diagnosis of undifferentiated CTD. CONCLUSIONS: Our results suggest that identification of anti-SSA antibody in patients with early ILD can reveal a specific subgroup of patients with more ground glass opacity and more severe lung function impairment than those without anti-SSA antibody.

Tobacco-associated pulmonary vascular dysfunction in smokers: role of the ET-1 pathway.

Pulmonary vascular remodeling and dysfunction associated to tobacco smoking might pave the way for the subsequent development of pulmonary hypertension. Its prognosis is dreadful and its underlying mechanisms are so far largely unknown in humans. To assess the potential role of endothelin-1 and its receptors in smokers' pulmonary artery vasoactive properties. Endothelium-dependent vasodilation to ACh was assessed in pulmonary vascular rings from 34 smokers and compared with that of 10 nonsmokers. The effects of ET-A (BQ 123) or ET-B (BQ 788) blockers and that of an ET-B activator (sarafotoxin) were evaluated. Endothelin-1 was quantitated by ELISA. Expression of its receptors was quantitated by Western blotting. Smokers exhibited an impaired pulmonary endothelium-dependent vasodilation compared with nonsmokers (P < 0.01). In the former group, 8 of 34 subjects exhibited a marked endothelial dysfunction (ED(+)) whereas 26 (ED(-)) (P < 10(-4)) displayed a vasorelaxation to ACh that was comparable to that of nonsmokers. In ED(+) subjects, ET-A was overexpressed (P < 0.05) and inversely correlated (P < 10(-2)) with the response to ACh. Sarafotoxin significantly improved vasodilation in all subjects (P < 10(-2)). In conclusion, tobacco smoking is associated to an impaired pulmonary vasorelaxation at least partly mediated by an ET-1/ET-A-dependent dysfunction.

Association of ex vivo vascular and bronchial dysfunctions in smokers.

BACKGROUND: It has recently been shown that systemic endothelial dysfunction is associated with airflow limitation in COPD. We conducted this ex vivo study to assess whether endothelial dysfunction of pulmonary arteries of former smokers was associated with modifications of airway functions. METHODS: Pharmacological experiments were conducted on arterial and bronchial rings obtained from lung specimen of 20 patients: 13 smokers without COPD and 7 smokers with mild to moderate COPD (GOLD class I or II). The impairment of acetylcholine-mediated vasodilation (constriction) of preconstricted arterial rings defined endothelial dysfunction. Resting tone (initial and after a contraction test) and cGMP-mediated dilation of bronchial rings in response to zaprinast were evaluated. RESULTS: Initial airway resting tone was correlated with airflow limitation (FEV(1) % predicted: Rho = -0.49; p = 0.032). The acetylcholine response of arterial rings was correlated with zaprinast-induced bronchodilation (Rho = 0.54, p = 0.019). Patients with endothelial dysfunction (n = 5), as compared with those displaying no dysfunction (n = 15), were characterized by an increased resting tone (after contraction test), an impaired response to zaprinast but a similar degree of airflow limitation (FEV(1)). CONCLUSION: Endothelial dysfunction of pulmonary arteries is associated with increased resting tone and impaired cGMP-mediated dilation of airways in former smokers, suggesting common underlying mechanisms of pulmonary arterial and bronchial dysfunctions.