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The COPD Assessment Test (CAT): Short- and Medium-term Response to Pulmonary Rehabilitation.

The COPD Assessment Test (CAT) is a recently introduced instrument to assess health-related quality of life in COPD. We aimed to evaluate the longitudinal change in CAT following Pulmonary Rehabilitation (PR), and test the relationship between CAT and CRQ-Self Report (SR) over time.

We hypothesised that the CAT would show similar responsiveness to PR as the CRQ-SR both in the short and medium-term.

Methods: 118 COPD patients completed an eight-week outpatient multidisciplinary PR programme. CAT, CRQ-SR and the incremental shuttle walk (ISW) were measured prior to starting PR (T1), completion of PR (T2) and 6 months after completion of PR (T3).

Results: There was a significant improvement in CAT, CRQ-SR and ISW immediately following PR (p < 0.001). Although there was decline between T2 and T3, CAT, CRQ-SR and ISW remained significantly better at T3 compared with T1 (ANOVA p < 0.001). Both between T1-T2 and between T2-T3, change in CAT correlated significantly with change in CRQ (both r  = -0.44 and p < 0.001). The slope of the relationship between CAT change and CRQ-SR change at T1-T2 and T2-T3 was not significantly different (ANCOVA: intercept p  =  0.79, interaction effect p  =  0.95).

Conclusions: In COPD, the CAT score is immediately responsive to PR and remains improved at 6 months. There is no significant difference in the short and medium term changes in the CAT and CRQ-SR following PR. We propose that for most clinical indications for assessing health-related quality of life in COPD, the CAT is a robust and practical alternative to longer-established instruments such as the CRQ-SR.

Selective PDE inhibitors as novel treatments for respiratory diseases.

Phosphodiesterases (PDEs) are a family of enzymes which catalyse the metabolism of the intracellular cyclic nucleotides, c-AMP and c-GMP that are expressed in a variety of cell types and in the context of respiratory diseases, It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical benefit to patients with asthma or chronic obstructive pulmonary disease (COPD). The orally active PDE4 inhibitor Roflumilast-n-oxide has been approved for treatment of severe exacerbations of COPD as add-on therapy to standard drugs.

This review discusses the involvement of PDEs in airway diseases and various strategies that are currently being pursued to improve efficacy and reduce side-effects of PDE4 inhibitors, including delivery via the inhaled route, mixed PDE inhibitors and/or antisense biologicals targeted towards PDE4.

Indacaterol: A Novel Long-Acting β(2) -Agonist.

Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are β(2) -agonists and anticholinergics, either alone or in combination. Currently available β(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration.

Indacaterol is considered an ultra-long-acting β(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Cough was the most commonly reported adverse effect with use of indacaterol. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators.

Based on similar improvement in spirometric measurements compared with other bronchodilator drugs and the convenience of its once-daily dosing, indacaterol may be beneficial in the management of mild-to-moderate chronic obstructive pulmonary disease, either alone or in combination with anticholinergic drugs administered once/day.

Effect of Incremental Exercise on Airway and Systemic Inflammation in Patients with COPD.

Airway and systemic inflammation are features of chronic obstructive pulmonary disease (COPD) and there is growing interest in clarifying the inflammatory processes. Strenuous exercise induces an intensified systemic inflammatory response in patients with COPD, but no study has investigated the airway inflammatory and anti-inflammatory responses to exercise.

Twenty steroid-naïve, ex-smokers, with diagnosed COPD (FEV(1)=66±12%) underwent baseline collection of venous blood and induced sputum followed by an incremental exercise test to symptom limitation 48-hours later. Additional venous blood samples were collected following exercise at 0, 2 and 24-hours, while induced sputum was collected 2 and 24-hours after exercise. Sputum and blood samples were analyzed for differential cell count, CD4(+) and CD8(+) T-lymphocytes (serum only), interleukin (IL)-6, IL-8, IL-10, CCL5, and high sensitivity C-reactive protein (serum only).

There was an increase in the number of sputum eosinophils (cells/gram, p=0.012) and a reduction in sputum IL-6 (p=0.01) 24-hours post exercise. Sputum IL-8 and CCL5 were also persistently decreased after exercise (p=0.0098 and p=0.0012, respectively) but sputum IL-10 did not change. There was a decrease in serum eosinophils 2-hours after exercise (p=0.0014) and a reduction in serum CCL5 immediately following and 2-hours post exercise (p<0.0001). Both serum eosinophils and CCL5 returned to baseline-levels within 24-hours.

An acute bout of exercise resulted in a significant increase in the number of sputum eosinophils which may be mediated by serum CCL5. However, there was also a reduction in sputum pro-inflammatory cytokines, suggesting some anti-inflammatory effect of exercise in the lungs of steroid-naïve patients with COPD.

Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease.

THE AIMS OF THE STUDY WERE: (1) to compare numerical parameters of specific airway resistance (total, sRaw(tot), effective, sRaw(eff) and at 0.5 L · s(-1), sRaw(0.5)) and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs(0 Hz)], mean resistance [Rrs(mean)], and resistance/frequency slope [Rrs(slope)]) and (2) to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD).

METHODS: A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used. A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8) underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC) scale assessments.

RESULTS: Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance) and that resistance parameters of the two techniques were not equivalent, obviously. Correlative analyses further showed that Raw(tot) and Raw(eff) (and their specific resistances) can be considered as equivalent and correlated with indices that are considered to explore peripheral airways (residual volume (RV), RV/ total lung capacity (TLC), Rrs(slope)), while Rrs(mean) and Raw(0.5) explored more central airways. Only specific resistances taking into account the specific resistance loop area (sRaw(tot) and sRaw(eff)) and Rrs(slope) were statistically linked to dyspnea.

CONCLUSION: Parameters obtained from both body plethysmography and FOT can explore peripheral airways, and some of these parameters (sRaw(tot), sRaw(eff,) and Rrs(slope)) are linked to activity-related dyspnea in moderate to severe COPD patients.

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