Comparison of Δ FVC (% Decrease in FVC at the PC20) Between Cough-Variant Asthma and Classic Asthma

The percentage decrease in forced vital capacity (FVC) at the methacholine PC₂₀ (Δ FVC) has been proposed as a surrogate marker of maximal airway response. The aim of this study was to compare the Δ FVC between patients with cough-variant asthma (CVA) and those with classic asthma (CA). We performed a retrospective analysis of methacholine challenge test data from 47 children who were diagnosed as having CVA and from 75 children who had CA of mild severity. The mean (± SD) Δ FVC was significantly (p = 0.001) lower in the CVA group (14.7 ± 3.4%) compared with the CA group (17.1 ± 4.4%), whereas PC₂₀ was not different between the two groups. Our results suggest that CVA is associated with a lower level of maximal airway response than CA.     

Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism

Introduction

Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment.

Materials and Methods

Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria.

Results

Physiological dead space (Vd/Vt) (34.5 ± 11.4 vs 50.8 ± 6.6 %, p < 0.001) and alveolar-arterial oxygen gradient (29 ± 16 vs 46 ± 12 mmHg, p < 0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC > 0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p = 0.08).

Conclusions

Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting.     

Continuous glucose monitoring in youth with cystic fibrosis treated with lumacaftor-ivacaftor

Background

The effects of lumacaftor-ivacaftor therapy on glycemia have not been thoroughly investigated. Continuous glucose monitoring (CGM) provides detailed information about glycemic patterns and detects glucose abnormalities earlier than traditional screening tools for diabetes.

Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate with pulmonary function decline

Background

To characterize glucose patterns with continuous glucose monitoring (CGM) in cystic fibrosis (CF) and assess relationships between CGM and clinical outcomes.

The FEV1/FEV6 ratio is a good substitute for the FEV1/FVC ratio in the elderly.

AIMS: To determine the agreement between the FEV1/FEV6 ratio and the FEV1/FVC ratio in an elderly population. METHOD: The study sample consisted of 3874 participants in a cross-sectional population survey in Troms?, Norway, aged 60 years or more, in whom acceptable spirometry had been obtained. Mean differences between the FEV1/FEV6 ratio (%) and the FEV1/FVC ratio (%) were calculated according to age, sex, smoking habit, and the degree of airflow limitation. ROC-curve analysis and Kappa-statistics were used to estimate the utility of the FEV1/FEV6 ratio in predicting an FEV1/FVC ratio < 70%. RESULTS: The mean difference between FEV1/FEV6% and FEV1/FVC% was 2.7% in both men and women. The difference between the two measures increased somewhat with increasing age, and was more pronounced with smoking and decreasing FEV1/FVC ratio. The value for the FEV1/FEV6 ratio which best predicted an FEV1/FVC ratio of 70%, was 73%, and a very good agreement was found between these two cut-off values (kappa = 0.86). CONCLUSION: The FEV1/FEV6 ratio appears to be a good substitute for the FEV1/FVC ratio in an elderly population.     

The prevalence of ibuprofen-sensitive asthma in children: a randomized controlled bronchoprovocation challenge study

OBJECTIVE: To determine the prevalence of ibuprofen-sensitive asthma in school-aged children with mild or moderate persistent asthma. STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover bronchoprovocation challenge study in children 6 to 18 years of age with mild or moderate persistent asthma. Patients received a single dose of ibuprofen or placebo, per randomization, and then returned 2 to 7 days later to repeat the procedures after taking that study drug not received at the first visit. At each visit, patients performed spirometry before and (1/2), 1, 2, and 4 hours after administration of study drug. We defined bronchospasm as a > or =20% decrease from baseline in the forced expired volume in the first second (FEV1) and ibuprofen sensitivity as bronchospasm following administration of ibuprofen but not placebo. RESULTS: Of the 127 patients screened, 100 (mean age, 11 years) completed the study. Two patients met criteria for ibuprofen-sensitive asthma, resulting in a prevalence of 2% (95% CI: 0.2%-7%). Neither patient was known to have had any exposure to ibuprofen before the study. CONCLUSION: The prevalence of ibuprofen-sensitive asthma was low but non-zero in this group of children with mild or moderate asthma. The possibility of ibuprofen-induced bronchospasm should be considered before administering ibuprofen to children with asthma.     

Cardiovascular findings in very low birthweight schoolchildren with and without bronchopulmonary dysplasia

BACKGROUND: With the introduction of new therapies in peri- and neonatology, the clinical picture of bronchopulmonary dysplasia (BPD) seems to alter. The consequences of this "new BPD" are of interest. AIM: To evaluate cardiovascular findings during the surfactant era in very low birthweight (VLBW, birth weight < 1500 g) schoolchildren with and without BPD. METHODS: At 7-8 years of age, 34 VLBW children with BPD born in one hospital underwent blood pressure (BP) measurement, electrocardiography (ECG), two-dimensional Doppler and M-mode echocardiography, flow-volume spirometry and whole-body plethysmography. The age- and sex-matched control groups comprised 34 VLBW children without BPD (no-BPD group) and 34 term children (term group). RESULTS: The mean(SD) diastolic BP was significantly higher in the no-BPD than in the BPD group (65(9) vs. 59(8) mm Hg, p < 0.05). No clinically significant tricuspid regurgitations were found. The groups did not differ with respect to right ventricular systolic time intervals corrected for heart rate. The results of all M-mode measurements were within normal range. Compared to term controls, the BPD cases had lower mean(SD) forced expiratory flow in 1 s (90(14)% vs. 99(11)% of ref., p < 0.05) and more often high ratio of residual volume to total lung capacity (15(52%) vs. 4(13%), p < 0.01). No clinically significant correlations were found between current lung function and echocardiographic findings. CONCLUSION: In the surfactant era, school-aged VLBW survivors with and without BPD do not seem to evince indirect signs of elevated pulmonary pressure. The increased pulmonary vascular resistance associated with BPD appears to resolve with time more rapidly than abnormalities in respiratory function.     

Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase)

OBJECTIVE: To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I). STUDY DESIGN: This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test. RESULTS: The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects. CONCLUSIONS: In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile.