Airflow obstruction as a marker of adverse prognosis in rheumatoid arthritis.

Objectives: In our study, we explored the specific subgroup of patients with rheumatoid arthritis (RA) suffering from obstructive lung disease (OLD) and its impact on morbi-mortality. Methods: Our retrospective study included 309 patients suffering from RA with either obstructive (O-RA) or non-obstructive patterns (non-O-RA). OLD was defined based on the Tiffeneau index at the first available pulmonary functional test (PFT). Survival was then calculated and represented by a Kaplan-Meier curve. The comparison between the populations considered was performed by the Log-Rank test. Results: Out of the 309 RA patients, 102 (33%) had airway obstruction. The overall survival time was significantly lower in the O-RA group than in the non-O-RA group (n = 207) (p < 0.001). The median survival time was 11.75 years in the O-RA group and higher than 16 years in the non-O-RA group. Multivariate analysis identified OLD as an independent risk factor for mortality (HR 2.20; 95% CI 1.21-4.00, p < 0.01). Conclusion: Airway obstruction can be an independent risk factor of mortality in RA and should be considered as an early marker of poor prognosis. Further prospective longitudinal studies are required in order to determine the best clinical management for O-RA patients.

Combined obstructive airflow limitation associated with interstitial lung diseases (O-ILD): the bad phenotype ?

BACKGROUND: Patients suffering from combined obstructive and interstitial lung disease (O-ILD) represent a pathological entity which still has to be well clinically described. The aim of this descriptive and explorative study was to describe the phenotype and functional characteristics of a cohort of patients suffering from functional obstruction in a population of ILD patients in order to raise the need of dedicated prospective observational studies and the evaluation of the impact of anti-fibrotic therapies. METHODS: The current authors conducted a retrospective study including 557 ILD patients, with either obstructive (O-ILD, n = 82) or non-obstructive (non O-ILD, n = 475) pattern. Patients included were mainly males (54%) with a mean age of 62 years. RESULTS: Patients with O-ILD exhibited a characteristic functional profile with reduced percent predicted forced expired volume in 1 s (FEV1) [65% (53-77) vs 83% (71-96), p < 0.00001], small airway involvement assessed by maximum expiratory flow (MEF) 25/75 [29% (20-41) vs 81% (64-108), p < 0.00001], reduced sGaw [60% (42-75) vs 87% (59-119), p < 0.01] and sub-normal functional residual capacity (FRC) [113% (93-134) vs 92% (75-109), p < 0.00001] with no impaired of carbon monoxide diffusing capacity of the lung (DLCO) compared to those without obstruction. Total lung capacity (TLC) was increased in O-ILD patients [93% (82-107) vs 79% (69-91), p < 0.00001]. Of interest, DLCO sharply dropped in O-ILD patients over a 5-year follow-up. We did not identify a significant increase in mortality in patients with O-ILD. Interestingly, the global mortality was increased in the specific sub-group of patients with O-ILD and no progressive fibrosing ILD phenotype and in those with connective tissue disease associated ILD especially in case of rheumatoid arthritis. CONCLUSIONS: The authors individualized a specific functional-based pattern of ILD patients with obstructive lung disease, who are at risk of increased mortality and rapid DLCO decline over time. As classically those patients are excluded from clinical trials, a dedicated prospective study would be of interest in order to define more precisely treatment response of those patients.

Breathomics to diagnose systemic sclerosis using thermal desorption and comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry.

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early diagnosis and prognosis associated with the disease progression are highly needed. Volatile organic compounds in exhaled breath are widely available and non-invasive and have the potential to reflect metabolic processes occurring within the body. Comprehensive two-dimensional gas chromatography coupled to high-resolution mass spectrometry was used to investigate the potential of exhaled breath to diagnose systemic sclerosis. The exhaled breath of 32 patients and 30 healthy subjects was analyzed. The high resolving power of this approach enabled the detection of 356 compounds in the breath of systemic sclerosis patients, which was characterized by an increase of mainly terpenoids and hydrocarbons. In addition, the use of 4 complementary statistical approaches (two-tailed equal variance t-test, fold change, partial least squares discriminant analysis, and random forest) resulted in the identification of 16 compounds that can be used to discriminate systemic sclerosis patients from healthy subjects. Receiver operating curves were generated that provided an accuracy of 90%, a sensitivity of 92%, and a specificity of 89%. The chemical identification of eight compounds predictive of systemic sclerosis was validated using commercially available standards. The analytical variations together with the volatile composition of room air were carefully monitored during the timeframe of the study to ensure the robustness of the technique. This study represents the first reported evaluation of exhaled breath analysis for systemic sclerosis diagnosis and provides surrogate markers for such disease.