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Highlights: [•] We investigated whether substance P modulates the perception of breathlessness in patients with chronic obstructive pulmonary disease. [•] Aprepitant, an antagonist that blocks neurokinin (NK)-1 receptor signaling, or placebo was administered prior to resistive load breathing. [•] Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. [•] With aprepitant, but not with placebo, blood levels of substance P (+54%) and beta-endorphin (+27%) increased. [•] The co-transmission of substance P (excitatory) and beta-endorphin (inhibitory) neuropeptides presumably reflects an integrated response. [ABSTRACT FROM AUTHOR]

Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.Methods: Through a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza.Results: Twenty-fi ve trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment, ICS treatment was associated with a significantly higher risk of TB (Peto OR, 2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24;95% CI, 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore, the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667, respectively).Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD, which deserve further investigation. [ABSTRACT FROM AUTHOR]

The article discusses a study that evaluated the association of risks for influenza and tuberculosis (TB) in patients who have chronic obstructive pulmonary disorder (COPD) with treatment of inhaled corticosteroids (ICS). Compared were estimates of non-ICS treatment with ICS regimen for influenza and TB risks. Results showed higher risk of TB for patients with ICS treatment but not for influenza and lower TB events for COPD patients who have undergone ICS treatment in endemic areas.

Abstract: Background: Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms. Methods: A post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 μg) and open-label tiotropium (18 μg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = ‘less dyspnoea’; scores ≥2 = ‘more dyspnoea’). Outcomes were assessed after 26 weeks. Results: The analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose (‘trough’) forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) and St George''s Respiratory Questionnaire (SGRQ) total scores at week 26 and reduced the risk of COPD exacerbations vs placebo; and open-label tiotropium improved trough FEV1 and TDI total score vs placebo at week 26. In patients with more dyspnoea: indacaterol (both doses) improved trough FEV1, TDI and SGRQ total scores at week 26; indacaterol 300 μg was the only treatment to improve the TDI total score by more than the minimum clinically important difference (≥1 point) vs placebo; and open-label tiotropium improved trough FEV1, TDI total score at week 26 and decreased the risk of COPD exacerbations vs placebo. In both subgroups, all treatments were well tolerated. Conclusions: In patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 μg may be a useful treatment option for patients with COPD who experience more severe breathlessness. [Copyright &y& Elsevier]

Background: Although opioid receptors are expressed broadly in the CNS and in peripheral sensory nerve endings including bronchioles and alveolar walls of the respiratory tract, it is unknown whether the modulatory effect of endogenous opioids on breathlessness occurs in the CNS or in the peripheral nervous system. The purpose of this investigation was to examine whether increased blood levels of β-endorphin modify breathlessness by a putative effect of binding to peripheral opioid receptors in the respiratory tract.Methods: Twenty patients with COPD (10 women and 10 men; age, 70 ± 8 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and unpleasantness of breathlessness ≥ 50 mm on a 100-mm visual analog scale. At two interventions, blood levels of β-endorphin and adrenocorticotropic hormone (ACTH) were measured, ketoconazole (600 mg) or placebo was administered orally, and patients rated the two dimensions of breathlessness each minute during resistive load breathing (RLB).Results: By inhibiting cortisol synthesis, ketoconazole led to significant increases in β-endorphin (mean change, 20% ± 4%) and ACTH (mean change, 21% ± 4%) compared with placebo. The intensity and unpleasantness ratings of breathlessness and the endurance time during RLB were similar in the two interventions.Conclusions: The previously demonstrated modulatory effect of endogenous opioids on breathlessness appears to be mediated by binding to receptors within the CNS rather than to peripheral opioid receptors in the respiratory tract. An alternative explanation is that the magnitude of the β-endorphin response is inadequate to affect peripheral opioid receptors.Trial Registry: ClinicalTrials.gov; No.: NCT01378520; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Abstract: Chronic obstructive pulmonary disease (COPD) is recognized by the Global Initiative for Chronic Obstructive Lung Disease guidelines as an inflammatory disease state, and treatment rationales are provided accordingly. However, not all physicians follow or are even aware of these guidelines. Research has shown that COPD inflammation involves multiple inflammatory cells and mediators and the underlying pathology differs from asthma inflammation. For these reasons, therapeutic agents that are effective in asthma patients may not be optimal in COPD patients. COPD exacerbations are intensified inflammatory events compared with stable COPD. The clinical and systemic consequences believed to result from the chronic inflammation observed in COPD suggest that inflammation intensity is a key factor in COPD and exacerbation severity and frequency. Although inhaled corticosteroids are commonly used and are essential in asthma management, their efficacy in COPD is limited, with only a modest effect at reducing exacerbations. The importance of inflammation in COPD needs to be better understood by clinicians, and the differences in inflammation in COPD versus asthma should be considered carefully to optimize the use of anti-inflammatory agents. [Copyright &y& Elsevier]

The article offers information on the use of indacaterol along with tiotropium in patients suffering from with chronic obstructive pulmonary disease (COPD). It informs that the method helps in increasing the caliber of a bronchial tube. It also informs that administration of indacaterol and tiotropium is an effective treatment strategy for patients with COPD.

The article discusses a study which investigated differences in ventilatory responses and gas exchange as proposed mechanisms for such an observation. The researchers measured arterial blood gas and lactate levels in 12 patients with chronic obstructive pulmonary disease (COPD) during incremental treadmill and cycle exercise. It was found that partial pressures of alveolar and artificial oxygen in patients was significantly lower at peak exercise for treadmill walking.

The article examines the validity of the hypothesis that patients with chronic obstructive pulmonary disease will show more improvement in exercise endurance and breathlessness relief with bronchodilator therapy if they exercise by treadmill walking instead of cycling. According to the authors, differences in physiologic and perceptual responses with bronchodilation showed that treadmill walking has an advantage as an exercise stimulus.