The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
-
Randomized Controlled Trial Multicenter Study
A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations.
Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD). The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. ⋯ FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.
-
The role of mannose-binding lectin (MBL) deficiency (MBL2; XA/O and O/O genotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located near MBL2, are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes. ⋯ We showed the existence of LD between MBL2 and SP genes. The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD among MBL2 and SP genes must be considered in studies on the role of MBL in infectious diseases.
-
Severe sepsis is one of the most common causes of acute lung injury (ALI) and is associated with high mortality. The aim of the study was to see whether a protective strategy based approach with a plateau pressure <30 cmH(2)O was associated with lower mortality in septic patients with ALI in the Surviving Sepsis Campaign international database. A retrospective analysis of an international multicentric database of 15,022 septic patients from 165 intensive care units was used. ⋯ In patients with ALI and mechanical ventilation, the use of inspiratory plateau pressures maintained at <30 cmH(2)O was associated with lower mortality by Chi-squared test (46.4% versus 55.1%, p<0.001) and by Kaplan-Meier and log-rank test (p<0.001). In a multivariable random-effects Cox regression, plateau pressure <30 cmH(2)O was significantly associated with lower mortality (hazard ratio 0.84, 95% CI 0.72-0.99; p=0.038). ALI in sepsis was associated with higher mortality, especially when an inspiratory pressure-limited mechanical ventilation approach was not implemented.
-
The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la); commonly estimated by pulmonary capillary wedge pressure: P(pcw)) has been recommended for the detection of intrinsic pulmonary vascular disease in left-heart conditions associated with increased pulmonary venous pressure. In these patients, a TPG of >12 mmHg would result in a diagnosis of "out of proportion" pulmonary hypertension. This value is arbitrary, because the gradient is sensitive to changes in cardiac output and both recruitment and distension of the pulmonary vessels, which decrease the upstream transmission of P(la). ⋯ It may, therefore, be preferable to rely on a gradient between diastolic P(pa) and P(pcw). The measurement of a diastolic P(pa)/P(pcw) gradient (DPG) combined with systemic blood pressure and cardiac output allows for a step-by-step differential diagnosis between pulmonary vascular disease, high output or high left-heart filling pressure state, and sepsis. The DPG is superior to the TPG for the diagnosis of "out of proportion" pulmonary hypertension.
-
Exhaled nitric oxide fraction (F(eNO)) has been proposed as a noninvasive marker of eosinophilic bronchial inflammation in active asthma, and supposed to reflect responsiveness to corticosteroid therapy. There are several factors influencing F(eNO), and its role in early childhood respiratory disorders needs to be established. Between 2004 and 2008, 444 children aged <3 yrs with recurrent lower respiratory tract symptoms were referred to a tertiary centre for further investigation. 136 full-term, steroid-free, infection-free infants, median age of 16.4 months (range 4.0-26.7 months), successfully underwent measurement of F(eNO), lung function tests, and a dosimetric methacholine challenge test. ⋯ Elevated F(eNO) (≥ 27 ppb, the highest quartile) was associated with maternal history of asthma (adjusted OR 3.2, 95% CI 1.3-8.1; p=0.012), and increased airway responsiveness (the provocative dose of methacholine causing a 40% fall in maximal expiratory flow at functional residual capacity ≤ 0.30 mg) (adjusted OR 4.1, 95% CI 1.4-12.7; p=0.012). Atopy, blood eosinophilia and lung function were not associated with elevated F(eNO). In conclusion, maternal history of asthma, and increased airway responsiveness are associated with elevated F(eNO) in infants with recurrent lower respiratory tract symptoms.