Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD

Background and objective:   Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin-releasing hormone receptor 1 ( CRHR1 ) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single-nucleotide CRHR1 polymorphisms in patients with COPD.
Methods:   COPD patients ( n  = 87) with a positive smoking history were recruited from the pulmonary clinics of 11 hospitals in Korea. Patients were treated with fluticasone propionate and salmeterol for 12 weeks and lung function was measured at baseline and after the 12-week treatment. Eighty-four of the 87 subjects were successfully genotyped.
Results:   Seventy-one patients with the wild-type GG genotype and 13 patients with the heterozygous GT genotype in rs242 941 were evaluated. After 12-week treatment, the change in FEV₁ was significantly higher in patients with wild-type GG genotype (6.0 ± 0.8% of predicted FEV₁) than in GT heterozygotes (−0.8 ± 1.8, P  = 0.003).
Conclusions:   Improved FEV₁ following inhaled corticosteroid and a long-acting β2-agonist was associated with CRHR1 genetic polymorphism in patients with COPD.     

Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography

Background and objective:   Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross-sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function.
Methods:   Eighty-three men with COPD had completed five annual assessments of CT scans and pulmonary function tests over 4 years. Airway dimensions of the basal segment bronchi and lung attenuation on CT images were analysed in 38 subjects in whom the same airway could be measured at least three times, including at entry and at the end of the study.
Results:   Mean annual decline in FEV₁ was 21 mL/year. Annual changes in the percentage of low attenuation areas were not significantly correlated with decline in FEV₁. On the other hand, annual changes in the percentage of wall area (WA%/year) were significantly inversely correlated with annual changes in FEV₁ ( r  = −0.363, P  = 0.025), whereas WA%/year did not differ among severity stages at entry and did not correlate with baseline FEV₁.
Conclusions:   The results showing that annual changes in airway thickening correlated with annual decline in air flow limitation suggests the importance of treatment of airway inflammation in COPD. CT is a useful tool for quantitative estimation not only of emphysema but also of airway lesions in longitudinal studies.     

Airway responses to salbutamol after exposure to chemical warfare

Background and objectives:   Increased airway responsiveness to β-agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β-agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.
Methods:   The threshold concentrations of inhaled salbutamol required for a 20% change in FEV₁ as PC₂₀, or a 35% change in specific airway conductance (sGaw) as PC₃₅ were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.
Results:   In 11 of the 22 subjects PC₂₀ salbutamol could be measured and in 15 of the 22 subjects PC₃₅ salbutamol could be measured. This group of patients was the responder group (PC₂₀ = 10.79 and PC₃₅ = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC₂₀ = 237.68 and PC₃₅ = 88.72 mg/L, P  < 0.001). There was a significant correlation between FEV₁ and PC₂₀ salbutamol ( r  = 0.815, P  < 0.001).
Conclusions:   These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.     

Choice of spirometric reference values for compensation assessment

Background and objective:   Two sets of local reference values are available for spirometry in Hong Kong, but it is uncertain how well they work in the assessment of occupational lung diseases. This study examined their relative performance in the compensational assessment of silicosis.
Methods:   Local reference values published in 1982 and 2006 were compared in two different populations comprising normal construction/quarry workers and silicosis patients. Only men aged 20–74 years were included.
Results:   The FVC results of 93 normal workers were significantly higher than those predicted by either the 1982 or the 2006 reference values. Compared with the 1982 reference values, the mean FEV₁% or FVC% was age-dependent and 5.2% higher in the normal workers. Smoking decreased the forced expiratory ratio, but did not show a major effect on FEV₁ or FVC among asymptomatic subjects. Despite their derivation largely from never-smokers, the 2006 reference values better predicted FEV₁ and FVC among all smoking categories. Among the 357 silicosis patients, the 1982 reference values also gave 8.8% higher FEV₁% and 7.4% higher FVC%. These spirometric values differed by more than 10% in patients aged 60 years or more. Despite the presence of disease, the mean FVC% was still significantly above 100%.
Conclusions:   Both the 1982 and 2006 local reference values underestimated the FVC of normal construction and quarry workers, reflecting possible occupational selection factors. The 2006 reference values outperformed the 1982 ones, especially among older subjects. Careful calibration with similar occupational groups in the same laboratory is highly desirable in the choice of spirometric reference values for compensation assessment. Smoking does not appear to affect this choice.     

Correlation of C-reactive protein with disease severity in CT diagnosed emphysema

Background and objective:   Recent studies suggest that CRP levels are related to airflow obstruction. However, limited data exist on the relevance of CRP levels in individuals with or without emphysema. The aim of this study was to assess the relationship between the extent of emphysema, COPD severity and serum CRP levels.
Methods:   Lung function tests and high-sensitivity CRP were examined in 651 males with stable disease who underwent CT screening for lung cancer. CRP levels were examined cross-sectionally in individuals with various degrees of emphysema and in those without emphysema.
Results:   Emphysema was detected in 179 (34.7%) of 516 current smokers. Airflow obstruction was observed in 47 (28.8%) of 163 smokers with mild emphysema, in eight (57.1%) of 14 smokers with moderate emphysema, and in two of two individuals with severe emphysema. CRP levels were not higher in individuals with mild or moderate emphysema compared with individuals without emphysema. Among 98 individuals with airflow obstruction (19.0% of the 516 current smokers), there was a modest correlation between CRP levels and FEV₁%.
Conclusions:   The severity of COPD varied in individuals with similar degrees of emphysema. CRP levels were not significantly higher in individuals with mild or moderate emphysema compared with individuals without emphysema but CRP levels were modestly correlated with FEV₁% among individuals with airflow obstruction.     

Chronic obstructive pulmonary disease and interstitial lung disease in patients with lung cancer

Background and objective:   Although lung cancer is frequently accompanied by COPD and interstitial lung disease (ILD), the precise coincidence of these diseases with lung cancer is not well understood. The objectives of this study were to determine the prevalence of abnormal CT and spirometric findings suggestive of COPD or ILD in a population of patients with untreated lung cancer, and to estimate the lung cancer risk in this population.
Methods:   The study population consisted of 256 patients with untreated lung cancer and 947 subjects participating in a CT screening programme for lung cancer. Semi-quantitative analysis of low attenuation area (LAA), fibrosis and ground glass attenuation (GGA) on CT was performed by scoring. Gender- and age-matched subpopulations, with stratification by smoking status, were compared using the Mantel–Haenszel projection method.
Results:   Inter-observer consistency was excellent for LAA, but not as good for fibrosis or GGA scores. Pooled odds ratios for lung cancer risk using LAA, fibrosis, GGA scores and reduced FEV₁/FVC and %VC were 3.63, 5.10, 2.71, 7.17 and 4.73, respectively ( P  < 0.0001 for all parameters). Multivariate regression analyses confirmed these results.
Conclusion:   Abnormal CT and spirometric parameters suggestive of COPD and ILD were strong risk factors for lung cancer, even after adjusting for gender, age and smoking status.     

Protein malnutrition in elderly patients with chronic obstructive pulmonary disease

Background: It has been suggested that hypermetabolism or reduction of total caloric intake or a combination of both conditions occur in malnourished patients with chronic obstructive pulmonary disease (COPD). It is hypothesized that protein malnutrition plays a role in the metabolism of malnourished elderly COPD patients.
Methods: Thirteen COPD patients (mean age: 75.7 years) with severe obstructive ventilatory disorder were divided into two groups: body mass index greater than 20 (group N; n  = 8) and less than 20 (group L; n  = 5). A nutritional survey and metabolic study were performed.
Results: Energy balances appeared more highly positive in group L than in group N and serum concentrations of total protein, albumin and transferrin tended to be lower in group L than in group N (all showed no statistically significant difference). The mean protein digestibility did not show any significant difference between the two groups, suggesting that group L subjects digested and absorbed the ingested dietary protein normally. Mean nitrogen balance was more highly positive in group L than in group N. The FEV₁ decreased significantly with increases in the basal metabolic rate (BMR), total daily energy expenditure and urinary nitrogen excretion, respectively (all P  < 0.05). PaO₂ was positively and significantly correlated with serum concentrations of albumin and transferrin ( P  = 0.001 and P  < 0.05), respectively. Body mass index (BMI) was negatively correlated with BMR ( P  < 0.05).
Conclusions: It is suggested that malnourished COPD patients with lower BMI showed enhanced protein and energy metabolism. Thus, it is likely that malnourished elderly COPD patients could improve through not only supplementation of total carolic intake but also sufficient protein intake.     

Respiratory infections and lung function in an Australian Aboriginal community

Background and objective:   To investigate the association between serological evidence of past infections with common respiratory pathogens and lung function in members of an isolated community of Aborigines from tropical coastal north-western Australia.
Methods:   FEV₁ and FVC were assessed by dry bellows spirometer. Serum IgG titres to 11 common respiratory pathogens were assayed. Smoking history was assessed by questionnaire. Reciprocal positive IgG titres were taken as ≥10 for all pathogens with the exception of Legionella spp. (≥40) and Burkholderia pseudomallei (≥20). Linear regression analysis examined associations between titres and lung function after adjustment for age, height, gender and smoking, separately for adults (age > 17 years) and children.
Results:   An increased total number of positive IgG titres was significantly associated with reduced FEV₁ ( P  = 0.01) and FEV₁/FVC ratio ( P  = 0.01) suggesting the presence of airflow obstruction. This association was independent of age, gender, height, weight and smoking status.
Conclusions:   The burden of past respiratory infections may be an important determinant of airway function in this Aboriginal community.     

The effects of nebulised isotonic saline and terbutaline on breathlessness in severe chronic obstructive pulmonary disease (COPD)

Background: There is anecdotal evidence that nebulised saline relieves breathlessness at rest in patients with severe chronic obstructive pulmonary disease (COPD). It is unclear whether nebulised beta agonists are any more effective than nebulised saline in relieving breathlessness at rest in these individuals.
Aim: To compare the effects of nebulised saline and nebulised terbutaline on breathlessness at rest in patients with severe COPD.
Methods: We studied 18 patients with severe COPD with a mean age of 71.1 years, forced expiratory volume in 1 second (FEV₁) of 0.58 L and vital capacity (VC) of 1.59 L, in a randomised, double-blind, crossover trial. The subjects received three doses of nebulised saline on one study day, and three doses of nebulised terbutaline (cumulative dose 10 mg) on the other. Breathlessness was measured using Likert and Visual Analogue Scales (VAS).
Results: Both treatments led to a significant improvement in breathlessness on VAS and Likert scales but there was no significant difference in breathlessness scores for saline compared with terbutaline. There was a small but significant increase in FEV₁ with terbutaline of 74 mL, but no change with saline.
Conclusions: A saline aerosol has no effect on lung function but reduces breathlessness at rest in subjects with severe COPD. Nebulised saline may be considered as an adjunct to the use of nebulised bronchodilators for the treatment of breathlessness in patients with COPD.     

Small airways obstruction syndrome in clinical practice

Background and objective:   Small airways obstruction syndrome (SAOS) is a particular pulmonary function test (PFT) pattern showing decreased VC and FEV₁ but a normal FEV₁/VC ratio and TLC. The significance of this syndrome in clinical practice has not been comprehensively investigated.
Methods:   This study retrospectively identified all patients who had performed PFT that showed a SAOS pattern at a university teaching hospital over 1 year. A simple algorithm for differential diagnosis was developed and validated.
Results:   Of the 3207 PFT performed, 153 (4.8%) showed a pattern indicating SAOS. Among these, a final diagnosis was confirmed for 85 (63.4%) of the patients. The causes of SAOS included both restrictive and obstructive lung diseases with the leading causes being early interstitial lung disease ( n  = 20; 23.3%), chest wall deformity ( n  = 12; 14.1%) and asthma ( n  = 10; 11.6%). Using a cut-off point of TLC of <95% predicted value to identify restrictive ventilatory defects ( P  = 0.002) and of ≥95% predicted combined with RV/TLC ≥55% to identify obstructive ventilatory defects ( P  < 0.001), a simplified algorithm with good accuracy (86.6%) was identified. Validation in an independent group showed accuracy of 91%.
Conclusions:   The PFT pattern called SAOS is not uncommon. The most common causes of SAOS were early interstitial lung disease, chest wall deformity and asthma. A diagnostic algorithm was proposed, which may help physicians' decision-making in their daily practice.     

Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Background and objective:   Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients.
Methods:   COPD patients with pulmonary hyperinflation ( n  = 54) and healthy subjects ( n  = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein.
Results:   COPD patients had less diaphragm mobility than did healthy individuals (36.5 ± 10.9 mm vs 46.3 ± 9.5 mm, P  = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r  = −0.60, P  < 0.001; RV/TLC: r  = −0.76, P  < 0.001), moderately with airway obstruction (FEV₁: r  = 0.55, P  < 0.001; airway resistance: r  = −0.32, P  = 0.02) and weakly with pulmonary hyperinflation (TLC: r  = −0.28, P  = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r  = −0.11, P  = 0.43; maximal expiratory pressure: r  = 0.03, P  = 0.80).
Conclusion:   The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.     

Poor interpretation of pulmonary function tests in patients with concomitant decreases in FEV1 and FVC

Background and objective:   A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV₁ and FVC.
Methods:   A retrospective study was conducted of 681 patients with normal FEV₁/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy.
Results:   The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; P  < 0.0001).
Conclusions:   The weak agreement between the clinical diagnosis and the PFT interpretation in patients showing concomitant decreases in FEV₁ and FVC suggests that other clinical findings should be assessed in addition to PFT.     

Frequency of dosing and comparative doses of mometasone furoate: A meta-analysis

Background and objective:   To examine the evidence for the efficacy of once daily dosing of mometasone furoate (MF) and to establish the dose–response relationship for MF in asthma.
Methods:   Meta-analysis of double-blind, randomized controlled clinical trials, identified through a Medline and EMBASE search, comparing once versus twice daily dosing with the same dose and/or comparing two different doses that presented data on measurements of clinical efficacy. Main outcome measures were FEV₁ change from baseline, PEF, withdrawals for any reason and treatment failure as defined by the authors.
Results:   Nine studies with 2533 subjects were identified, although not all had usable data for the different doses/schedules. There was no evidence of superiority of twice versus once daily dosing of MF with a pooled difference of 0.02 L (95% CI: −0.06–0.10) for FEV₁ change from baseline. 400 µg was superior to 200 µg with a pooled difference of 0.09 L (95% CI: 0.04–0.13) for FEV₁. Data on doses >400 µg/day were limited but did not support that 800 µg was superior to 400 µg.
Conclusions:   For the outcome variables considered, once daily dosing of MF is as effective as twice daily dosing, which may be useful in improving compliance in the treatment of asthma. There was insufficient data to compute a dose–response curve for MF.     

Decline of outpatient asthma management in Argentina

Background and objectives:   To assess management of adult patients admitted with acute asthma and compare the results obtained with a similar study 5 years earlier.
Methods:   A cross-sectional survey of 211 consecutive patients admitted to hospital during a 12-month period was conducted. Patients were surveyed using a validated management questionnaire and the results compared with those of the previous survey.
Results:   There were 211 patients in the present survey and patient demographics were similar in both populations studied. Comparison of the previous to the current survey showed significant differences in predicted FEV₁% at admission (30.2 ± 10.7 vs 23.9 ± 8.9, respectively, P  < 0.001), and the average number of hospital admissions in the year prior to the survey (0.7 ± 1.2 vs 1.3 ± 0.7, P  < 0.0001). In the present survey, more patients changed their medication after acute exacerbation and more received an action plan. Compared with the previous survey, there were no significant differences between the mean number of emergency department visits, need for mechanical ventilation, number of patients prescribed inhaled corticosteroids and other related variables.
Conclusion:   Compared with the previous study the severity of asthma at the time of admission was worse. Some of the recommended international asthma management programmes appear to have been followed.     

Acute effects of hyperoxia on resting pattern of ventilation and dyspnoea in COPD

Background and objective:   Hyperoxia has been shown to reduce resting ventilation, hyperinflation and dyspnoea in patients with severely hypoxaemic COPD. This study assessed the effects of hyperoxia on these resting measures in patients with COPD of varying disease severity and characterized those patients who responded.
Methods:   Measurements of dyspnoea (Borg score), oxyhaemoglobin saturation (SpO₂), inspiratory capacity (IC), minute ventilation, tidal volume, breathing and cardiac frequency were performed at rest in 51 patients with COPD while they breathed air and 44% oxygen, in a randomized double-blinded fashion.
Results:   Hyperoxia induced significant reductions in cardiac frequency and dyspnoea and a significant increase in SpO₂. No significant change was noted in IC for the group overall, and there was substantial inter-subject variation in this measurement. No significant changes were found in ventilation, and there was no correlation between change in dyspnoea and change in IC. In patients with moderate to severe airflow obstruction (FEV₁ < 70% predicted), a significant association was found between the degree of airflow obstruction and change in IC induced by hyperoxia.
Conclusions:   Hyperoxia improved dyspnoea but did not significantly alter resting pulmonary hyperinflation in a group of patients with COPD of varying severity. However, in a subset patients with moderate to severe airflow obstruction a relationship existed between the severity of airflow obstruction and volume response to hyperoxia.     

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD

Background and objective:   Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD.
Methods:   Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification.
Results:   Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O₂ uptake, maximal O₂ pulse, maximal dyspnoea index, ventilatory response (ΔVE/ΔVCO₂), O₂ cost of ventilation (VO₂/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO₂ among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups.
Conclusions:   The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.     

Gender crossover of lung function

Background:  Although standard values of lung function are used for screening pulmonary diseases, only a few studies have been reported in the elderly.
Methods:  In this study, lung function in subjects below and above 65 years of age was analysed and the decline in lung function was compared according to age, between those below and those above 65 years.
Results:  Lung function below 65 years declined more in males than in females in both vital capacity (VC) and forced expiratory volume in 1 s (FEV₁). The decline in lung function was greater in females more than 65 years of age, compared with those less than 65 years. In males, the decline in FEV₁ was less for those more than 65 years than for those below 65 years, although the decline in VC showed a similar tendency to that of females.
Conclusions:  Selective survival may influence lung function more in men than in women. The gender difference of survival should be considered when estimating standard values, such as lung function, in the elderly.     

Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics

Background and objective:   Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC₄ synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC₄ synthase gene polymorphisms, were also investigated.
Methods:   The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV₁ after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed.
Results:   Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC₄ synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment ( P  < 0.05).
Conclusions:   There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.     

Resistance and reactance in oscillation lung function reflect basal lung function and bronchial hyperresponsiveness respectively

Background and objective:   Currently there are few data available regarding the use of impulse oscillometry parameters to assess airflow obstruction during standardized methacholine challenge testing.
Methods:   Methacholine challenge tests were performed using impulse oscillometry and conventional spirometry in 64 healthy and 39 asthmatic children, in order to determine airway resistance ( R ) and reactance ( X ) at frequencies of 5–35 Hz, as well as FEV₁.
Results:   Baseline R and X were significantly different between the healthy and asthmatic children, with the most discriminating parameter being resistance at 5 Hz ( R 5). In asthmatic children BHR was well demonstrated by FEV₁, X 5 and X 10, but not by R 5. However, when the actual R 5 values obtained in this study were compared with the predicted values, there appeared to be differences in the lung function measures that corresponded to varying methacholine concentrations. In addition, the PC20_FEV₁ and PC70_ X 5 were significantly more sensitive than other parameters for methacholine challenge testing.
Conclusions:   Measuring resistance at 5 Hz using impulse oscillometry facilitates significant differentiation of baseline lung function between asthmatic and healthy children. Additionally, X may be a suitable replacement for PC20 in methacholine challenge testing.     

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.