Exercise performance improves in patients with COPD due to respiratory muscle endurance training.

BACKGROUND: Impaired exercise tolerance is frequently observed in patients with COPD. Respiratory muscle endurance training (RMET) by means of normocapnic hyperpnea can be used to improve respiratory muscle function and probably exercise capacity. RMET is not applied on a large scale because complicated equipment is needed to maintain carbon dioxide homeostasis during hyperpnea, which can also be done by enlarging the dead space of the ventilatory system by breathing through a tube. Therefore, tube breathing might be a new, inexpensive method for home-based RMET. The aim of this study was to assess whether home-based RMET by means of tube breathing improves endurance exercise performance in patients with COPD. METHODS: We randomized 36 patients with moderate-to-severe COPD to RMET by paced tube breathing (n = 18) or sham training (control, n = 18). Both groups trained twice daily for 15 min, 7 days per week, for 5 weeks. RESULTS: Patients receiving RMET showed significant improvements in endurance exercise capacity (constant-load exercise on cycle ergometry; 18 min vs 28 min, p < 0.001), in perception of dyspnea (Borg score; 8.4 vs 5.4, p < 0.001), and respiratory muscle endurance capacity (sustainable inspiratory pressure; 25 cm H(2)O vs 31 cm H(2)O, p = 0.005). Quality of life (chronic respiratory disease questionnaire) also improved (78.7 to 86.6, p = 0.001). The control group showed no significant changes. CONCLUSION: Home-based RMET by means of tube breathing leads to a significant improvement of endurance exercise capacity, a reduction in perception of dyspnea, and an improvement in quality of life in patients with moderate-to-severe COPD.

Tube breathing as a new potential method to perform respiratory muscle training: safety in healthy volunteers.

Normocapnic hyperpnea has been established as a method of respiratory muscle endurance training (RMET). This technique has not been applied on a large scale because complicated and expensive equipment is needed to maintain CO(2)-homeostasis during hyperpnea. This CO(2)-homeostasis can be preserved during hyperpnea by enlarging the dead space of the ventilatory system. One of the possibilities to enlarge dead space is breathing through a tube. If tube breathing is safe and feasible, it may be a new and inexpensive method for RMET, enabling its widespread use. The aim of this study was to evaluate the safety of tube breathing and investigate the effect on CO(2)-homeostasis in healthy subjects. A total of 20 healthy volunteers performed 10 min of tube breathing (dead space 60% of vital capacity). Oxygen-saturation, PaCO(2), respiratory muscle function, hypercapnic ventilatory response and dyspnea (Borg-score) were measured. Tube breathing did not lead to severe complaints, adverse events or oxygen desaturations. A total of 14 out of 20 subjects became hypercapnic (PaCO(2)>6.0 kPa) during tube breathing. There were no significant correlations between PaCO(2) and respiratory muscle function or hypercapnic ventilatory responses. The normocapnic versus hypercapnic subjects showed no significant differences between decrease in oxygen saturation (-0.7% versus -0.2%, respectively, P=0.6), Borg score (4.3 versus 4.7, P=0.9), respiratory muscle function nor hypercapnic ventilatory responses. Our results show that tube breathing is well tolerated amongst healthy subjects. No complaints, nor desaturations occurred. Hypercapnia developed in a substantial number of subjects. When tube breathing will be applied as respiratory muscle training modality, this potential development of hypercapnia must be considered.

Vocational and working career of asthmatic adolescents is only slightly affected.

INTRODUCTION: The aim of this study was to investigate whether teenagers and adolescents (10-22 years) with asthma or asymptomatic bronchial hyperresponsiveness, were more likely to experience vocational or professional career limitations in the future, as compared to non-asthmatic contemporaries. METHODS: Data were used from a 14-year follow-up study in general practice, investigating the relationship between respiratory health in childhood and adolescence. At follow-up, the respiratory health status and information about career limitations were obtained. RESULTS: There were no statistical significant differences between asthmatics (n=52) and non-asthmatics (n=154) in the proportion currently employed subjects, or contract type. Most examined career limitations were infrequently reported in both groups, but seemed to occur slightly more frequent among asthmatics. Asthmatics seemed to have an increased risk for limitations in daily activities both attributable to their respiratory health (OR=2.6, 95% CI [1.0; 7.0]) and all-cause (OR=1.8, 95% CI [0.9; 3.3]), and for absence from work all-cause (OR=1.7, 95% CI [0.9; 3.3]). However, the differences were in most cases in the magnitude of only a few days per year. Neither lung function nor bronchial hyperresponsiveness did predict absence from work, or limitations in daily activities. CONCLUSION: Asthmatic young adults seem to experience somewhat more limitations in their vocational and professional careers. Nonetheless, the majority of the young asthmatics seem to be only slightly limited in their careers. In non-asthmatic young adults the presence of asymptomatic bronchial hyperresponsiveness does not seem to lead to career limitations.

Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia.

STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. METHODS: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.

Bronchial challenge, assessed with forced expiratory manoeuvres and airway impedance.

OBJECTIVE: The Methacholine concentration at which a 20% decrease of the forced expiratory volume in 1s (PC20_FEV1) or a 40% increase in airway resistance (PC40_Rrs6) occur are accepted indicators for airway hyperresponsiveness. We hypothesised that the level of detection of bronchial hyperresponsiveness will differ between the two methods. METHODS: The response to Methacholine was assessed by forced oscillation technique (FOT) and spirometry in 20 stable hyperresponsive asthmatics. The effects of repeated lung function measurements on respiratory muscle fatigue were measured from maximal inspiratory mouth pressure (MIP). After each dose, patients scored their perception of dyspnoea on a BORG scale. Differences in patient's burden were measured by comparing the BORG-score at PC40_Rrs6 (BORG-PC40_Rrs6) and at PC20_FEV1 (BORG-PC20_FEV1). Reproducibility was also evaluated. RESULTS: The PC20_FEV1-values were 2.2 (0.4) doubling dose higher as compared to the PC40_Rrs6 (P<0.001). The mean BORG-score at PC40_Rrs6 was 1.7 points lower as compared to the BORG-score at PC20_FEV1 (P<0.001). The difference (mean(sd)) between the PC20_FEV1 of measurement 1 and 2 was -0.1 (1.4) doubling dose, and -0.3 (2.7) doubling dose for PC40_Rrs6. The MIP after Methacholine provocation was 1.0(0.2) kPa lower as compared to the MIP before the challenge test (P<0.001), suggesting respiratory muscle fatigue. CONCLUSION: Measuring PC40_Rrs6 shortens the challenge test and lowers the concentrations of bronchoconstrictor agents as compared to measurements of PC20_FEV1. The FOT-method was less strenuous for patients. In spite of the fact that the reproducibility is two-fold worse than measuring PC20_FEV1, it still remains quite acceptable at a mean of 0.3 doubling dose. The respiratory muscle strength was deteriorated after the challenge test.

Sick leave in patients with obstructive lung disease is related to psychosocial and work variables rather than to FEV1.

The aim of this exploratory study was to investigate associations between sick leave in workers with asthma or COPD and disease-related variables, psychosocial variables, and work characteristics. Hundred and eighty-nine patients with physician-diagnosed asthma (N=118) or COPD (n=71) who had paid work in the past 12 months completed questionnaires on sick leave, health complaints, functional limitations, work characteristics and psychosocial issues, and underwent a pulmonary function test (FEV1 and FVC before and after bronchodilation). Logistic regression analyses were performed to investigate variables independently associated with high sick leave (i.e. more than twice a year and/or longer than 1 month per episode). Asthma patients, not having an emotionally difficult job, with low job satisfaction, who had changed employers, utilized job control, and who encountered pulmonary aggravating factors at work were found to have a higher incidence of sick leave. COPD patients, who had informed the employer or colleagues about the disease, who did not have difficult tasks at work, who did not hide dyspnea and limitations, and who reported high fatigue were showing higher sick leave. FEV1 and FVC were not associated with sick leave in either group. It was concluded that psychosocial variables, work characteristics, functional limitations, and complaints play a more important role in sick leave in workers with asthma and COPD than FEV1.

Knowledge about asthma and COPD: associations with sick leave, health complaints, functional limitations, adaptation, and perceived control.

We sought to investigate associations between knowledge about the disease and sick leave, health complaints, functional limitations, adaptation and perceived control. Patients with asthma (n = 101) and COPD (n = 64) underwent lung function tests and completed questionnaires. In addition, all were asked the question: 'what is the diagnosis of your disease?', with the response categories: 'asthma' and 'COPD (chronic bronchitis or emphysema)'. Thirty-five percent of the asthma patients and 30% of the COPD patients did not know their correct diagnosis. Sick leave was not associated with knowledge about the disease in asthma and COPD. In asthma, much knowledge about management of the disease was associated with better adaptation (P = 0.01) and less perceived control over health by external factors (P = 0.02). Knowing the correct diagnosis was associated with less control over health by powerful others (P = 0.02). For COPD, more knowledge about management of the disease was associated with better adaptation (P = 0.02) and less control over health by internal factors (P = 0.01). Knowing the correct diagnosis was associated with less control over dyspnea at work (P = 0.01).

Arterial baroreflex and peripheral chemoreflex function after radiotherapy for laryngeal or pharyngeal cancer.

PURPOSE: Denervation of the carotid sinus causes baroreflex and chemoreflex failure, resulting in labile hypertension and loss of hypoxic responsiveness. We investigated whether radiation therapy for laryngeal or pharyngeal cancer affects baroreflex and chemoreflex function. METHODS AND MATERIALS: Twelve patients were studied after radiation therapy for locally advanced laryngeal or pharyngeal cancer (11 male, 1 female, age: 56.0 +/- 7.9 years), 3.3 years (median; range 1.0-4.7) after radiotherapy and 15 healthy controls (11 male, 4 female, 53.4 +/- 9.2 years). We measured baroreflex sensitivity (phenylephrine), blood pressure level and variability (24-h Spacelabs and 5-h Portapres recordings), responses to cardiovascular reflex tests, and the ventilatory responses to normocapnic and hypercapnic hypoxia. RESULTS: Baroreflex sensitivity was lower in patients (9.7 +/- 7.8 ms/mm Hg) than in controls (17.5 +/- 10.3 ms/mm Hg, p = 0.011). Mean office blood pressure was significantly higher in patients (141.5 +/- 27.8/89.2 +/- 10.6 mm Hg, 63.3 +/- 12.3 bpm) than in controls (117.3 +/- 10.1/75.1 +/- 6.8 mm Hg, 61.8 +/- 10.8 bpm). Blood pressure variability was not different between groups, nor were the responses to reflex tests. The normo/hypercapnic ventilatory response to hypoxia was similar in patients (0.21 +/- 0.10/1.37 +/- 0.60 L/min/%) and controls (0.22 +/- 0.16/1.19 +/- 0.78 L/min/%). CONCLUSIONS: Radiation therapy for laryngeal or pharyngeal carcinoma does not affect chemoreflex function, but results in an attenuated baroreflex sensitivity. Clinically relevant blood pressure lability is absent however.

Discontinuation of furosemide decreases PaCO(2) in patients with COPD.

STUDY OBJECTIVE: To evaluate whether the discontinuation of furosemide treatment resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal oxygenation. BACKGROUND: Furosemide is widely prescribed in patients with COPD for the treatment of peripheral edema. It is known that furosemide causes a metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased alveolar ventilation. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, the Netherlands. PATIENTS: Twenty patients with stable COPD (10 men; median age, 70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70% predicted]). Subjects were included if they had received furosemide, 40 mg/d, for the treatment of peripheral edema for at least a month and if they had a mean nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left and/or right ventricular dysfunction, sleep apneas, and patients receiving other diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride replacement therapy, or long-term oxygen treatment were excluded. INTERVENTION: Furosemide was discontinued for 1 week and replaced by placebo treatment in the first or the second week. MEASUREMENTS AND RESULTS: Ventilation, daytime arterial blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and after 2 weeks. Sixteen subjects completed the study. Ventilation increased from 10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to 14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p < 0.01). Daytime and nocturnal oxygenation did not improve. CONCLUSIONS: Although it does not improve oxygenation, the discontinuation of furosemide decreases PaCO(2) in patients with COPD.

The course of inhalation profiles during an exacerbation of obstructive lung disease.

BACKGROUND: Acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are associated with increased airflow Limitation, hyperinflation and respiratory muscle fatigue. It is unclear, whether patients are able to perform adequate inhalations through various inhalation devices with different orfices during an exacerbation. The aim of this study was to examine the evolution of inhalation profiles of patients inhaling through Diskus, Turbuhaler, pressurized metered dose inhaler (pMDI) and Volumatic and consequently the appropriateness of using the various devices during an exacerbation. MEASUREMENTS: 15 hospitalized patients participated in this randomized comparison of inhalation profiles through the four placebo-devices. For each device, triplicate inhalation profiles were recorded during day 1-9 of admission and in stable phase (day 50). RESULTS: The mean percentage of patients performing optimum inhalation profiles was 100% for Diskus, 60% for Turbuhaler, 14% for pMDI and 87% for Volumatic over the interval of day 1-9 and day 50. Patients with an inspiratory muscle strength (MIP) of less than 6kPa were generally unable to generate the optimum flow through the Turbuhaler (>60 l/min). CONCLUSION: The Diskus and Volumatic can be used effectively in the acute phase of an exacerbation of asthma or COPD. The Turbuhaler could be optimally used after the fifth day of convalescence. The pMDI is rather unsuitable during an exacerbation.

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO(2)). Acute metabolic acidosis was induced by administration of ammonium chloride (NH(4)Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo-controlled cross-over design in 15 healthy subjects (4 male; age 33.2 +/- 11.5 years; FEV(1) 108.3 +/- 16.2% predicted), 14 asthma patients (5 male; age 48.1 +/- 16.1 years; FEV(1) 101.6 +/- 15.3% predicted), and 15 moderate to severe COPD patients (9 male; age 62.8 +/- 6.8 years; FEV(1) 50.0 +/- 11.8% predicted). An acute metabolic acidemia of BE -3.1 mmol x L(-1) was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference -0.1 kPa x sec x L(-1) [95%-CI: -0.1 - -0.02]. In COPD patients PaCO(2) was significantly lowered during metabolic acidemia (mean difference -1.73 mmHg [-3.0 - -0.08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.

Salbutamol pMDI gives less protection to methacholine induced airway obstruction than salbutamol via spacer or DPI.

BACKGROUND: Inhalation device and inhalation technique influence the deposition of drug in the lung. This study evaluated the efficacy of salbutamol as a bronchoprotective agent administered via Diskus, Turbuhaler, pMDI or pMDI + Volumatic against methacholine-induced bronchoconstriction. METHODS: Twenty stable asthmatics participated in this open randomised comparison of the protective effects of 200 microg salbutamol, administered via the various inhalation devices on methacholine-induced airway obstruction, with respect to pulmonary function and dyspnoea sensation. The inhalation technique was controlled by measuring the peak inspiratory flow (and actuation time, in the case of pMDI and Volumatic) through the device, during inhalation. RESULTS: Inhalation of salbutamol increased the provocative dose of methacholine by 1.2 doubling doses (dd) for pMDI, 1.9 dd for Diskus, 2.3 dd for Turbuhaler and 2.5 dd for Volumatic. Salbutamol via pMDI provided less protection from methacholine-induced airway obstruction than did salbutamol administered via Diskus, Turbuhaler or Volumatic (P<0.05). The inadequate pMDI use of 70% of our patients might contribute to a lower deposition of drug in the central airways, resulting in the lower protective effect. However, the PC20_FEV1 of the adequate- and inadequate pMDI users showed no significant difference. CONCLUSION: Salbutamol administered via pMDI gave less protection from methacholine-induced bronchoconstriction than did salbutamol via Diskus, Turbuhaler or Volumatic. This study suggests that the pMDI may be less suitable for protecting a patient against bronchoconstriction due to airway hyperresponsiveness.

Predictors of changes in sick leave in workers with asthma: a follow-up study.

OBJECTIVE: The aim of this prospective study was to investigate predictors of 1-year changes in sick leave in workers with asthma. METHODS: The initial cohort consisted of 111 workers with asthma. One-hundred and one participants completed the follow-up after 1 year. Self-reported sick leave over the past 12 months was reported at baseline and at follow-up. At the start of this study, all participants completed questionnaires on adaptation to functional limitations, psychosocial variables, working conditions, lung function characteristics, disease history characteristics, health complaints and functional limitations, and person characteristics ('potential predictors'). Three multivariate logistic regression models were calculated, with an increase in sick leave, a decrease in sick leave, and stable high sick leave as dependent (outcome) variables, and the potential predictors as independent (explanatory) variables. RESULTS: An increase in sick leave was predicted by a lower level of education and perceiving more functional limitations in activities of daily life. A decrease in sick leave was predicted by spending all energy at work less often and perceiving fewer health complaints in social activities (adaptation criteria 4 and 5). Stable high sick leave was predicted by less job satisfaction, perceiving more support from the employer and perceiving more health complaints in social activities (adaptation criterion 5). Lung function characteristics, or disease history characteristics were not predictive for changes in sick leave in any of the groups. CONCLUSION: We conclude that adaptation to functional limitations played a major role in changes in sick leave in workers with asthma. Lung function characteristics hardly played a role.