Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study.

BACKGROUND: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. PURPOSE: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. DESIGN: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. METHODS: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. RESULTS: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. CONCLUSION: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Diffusing capacity for carbon monoxide is linked to ventilatory demand in patients with chronic obstructive pulmonary disease.

Dyspnea is deemed to result from an imbalance between ventilatory demand and capacity. The single-breath diffusing capacity for carbon monoxide (DLCO) is often the best correlate to dyspnea in COPD. We hypothesized that DLCO contributes to the assessment of ventilatory demand, which is linked to physiological dead space /tidal volume (V(D)/V(T)) ratio. An additional objective was to assess the validity of non-invasive measurement of transcutaneous P(CO2) allowing the calculation of this ratio. Forty-two subjects (median [range] age: 66 [43-80] years; 12 females) suffering mainly from moderate-to-severe COPD (GOLD stage 2 or 3: n = 36) underwent pulmonary function and incremental exercise tests while taking their regular COPD treatment. DLCO% predicted correlated with both resting and peak physiological V(D)/V(T) ratios (r = -0.55, p = 0.0015 and r = -0.40, p = 0.032; respectively). The peak physiological V(D)/V(T) ratio contributed to increase ventilation (increased ventilatory demand), to increase dynamic hyperinflation and to impair oxygenation on exercise. Indirect (MRC score) and direct (peak Borg score/% predicted VO(2)) exertional dyspnea assessments were correlated and demonstrated significant relationships with DLCO% predicted and physiological V(D)/V(T) at peak exercise, respectively. The non-invasive measurement of transcutaneous P(CO2) both at rest and on exercise was validated by Bland-Altman analyses. In conclusion, DLCO constitutes and indirect assessment of ventilatory demand, which is linked to exertional dyspnea in COPD patients. The assessment of this demand can also be non invasively obtained on exercise using transcutaneous PCO(2) measurement.

Too rapid increase and too much breathlessness are distinct indices of exertional dyspnea in COPD.

To assess whether different indices of dyspnea can be obtained from cardiopulmonary exercise test and whether these indices correlate with distinct physiological parameters in COPD. Forty-two COPD patients (12 females, median [IQ] age 66 [56-70] years; FEV(1)% predicted: 51 [38-65]) underwent pulmonary function and incremental exercise tests. A power law function described the oxygen consumption (V(O2)-Dyspnea relationship from which two indices correlated with MRC score: dyspnea score measured at 50% of predicted V(O2) (too much breathless for that effort) and tangent measured at 50% of peak dyspnea (too rapid increase in dyspnea at this time point). The former independently correlated with ventilation on exercise, while the latter independently correlated with baseline hyperinflation. An upward shift of both (iso)-V(O2) and -ventilation was evidenced in patients with higher levels of dyspnea (MRC score ≥ 3) and their tangents were significantly different. In conclusion, baseline hyperinflation is associated with the perception of a too rapid increase in dyspnea on exercise in COPD.