David C. Todd

Altered respiratory physiology in obesity.

The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.

Effect of obesity on airway inflammation: a cross-sectional analysis of body mass index and sputum cell counts.

Background Several observational studies have demonstrated an association between obesity and asthma. Studies evaluating exhaled nitric oxide levels and obesity have revealed that a higher body mass index (BMI) is associated with elevated exhaled nitric oxide levels. Airway inflammation using sputum cell counts has not been assessed in obese patients with airway diseases.

Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease - practical issues: A Canadian Thoracic Society Clinical Practice Guideline

Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific aspects of PR programming including optimal site of rehabilitation delivery, components of rehabilitation programming, duration of rehabilitation, target populations and timing of rehabilitation. The present document was compiled to specifically address these important clinical issues, using an evidence-based, systematic review process led by a representative interprofessional panel of experts. The evidence reveals there are no differences in major patient-related outcomes of PR between nonhospital- (community or home sites) or hospital-based sites. There is strong support to recommend that COPD patients initiate PR within one month following an acute exacerbation due to benefits of improved dyspnea, exercise tolerance and health-related quality of life relative to usual care. Moreover, the benefits of PR are evident in both men and women, and in patients with moderate, severe and very severe COPD. The current review also suggests that longer PR programs, beyond six to eight weeks duration, be provided for COPD patients, and that while aerobic training is the foundation of PR, endurance and functional ability may be further improved with both aerobic and resistance training.

Antiinflammatory Effects of Long-Acting β2-Agonists in Patients With Asthma: A Systematic Review and Metaanalysis

Background Long-acting β 2 -agonists are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. Methods A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. Results Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. Conclusion LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.BACKGROUND Long-acting beta(2)-agonists (LABAs) are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. METHODS A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. RESULTS Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. CONCLUSION LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.

Original ResearchAsthmaAntiinflammatory Effects of Long-Acting β2-Agonists in Patients With Asthma: A Systematic Review and Metaanalysis

Background Long-acting β 2 -agonists are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. Methods A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. Results Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. Conclusion LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.BACKGROUND Long-acting beta(2)-agonists (LABAs) are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. METHODS A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. RESULTS Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. CONCLUSION LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.

Importance of dosimeter calibration method on nebulizer output

BACKGROUND We have observed that dosimeter-run nebulizers have a much smaller output when manually activated than when breath activated; however, this has not been adequately investigated. OBJECTIVE To evaluate the effect of different calibration methods on nebulizer output. METHODS Six healthy subjects performed all calibrations. The nebulizers were operated by 2 different dosimeters and were calibrated to produce 9 microL per actuation by breath activation followed by exhalation to the room. The nebulizers were then operated at these identical settings, and the output determined in 3 ways: (1) breath activation followed by exhalation to the room, (2) breath activation with exhalation into the nebulizer, and (3) manual activation (with no subject using the nebulizer). These 3 methods were termed regular, rebreathe, and manual, respectively. RESULTS There was a large and statistically significant difference in nebulizer output among the 3 methods. The measured rebreathe outputs (5.6 and 5.7 microL per actuation) were approximately two thirds and the manual outputs (3.2 and 3.9 microL per actuation) were approximately one third of the regular calibration outputs (8.6 and 8.9 microL per actuation); the 2 values are for the 2 dosimeters. The results were highly statistically significant (P < .001). CONCLUSIONS The method by which a nebulizer-dosimeter system is calibrated results in different nebulizer outputs. This has a high likelihood of influencing the concentration of methacholine causing a 20% decrease in volume in the first second of forced expiration.