Dead-Space Ventilation Indices and Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) is associated with high ventilation-perfusion heterogeneity and dead-space ventilation. However, whether the degree of dead-space ventilation is associated with outcomes is uncertain. In this systematic review and meta-analysis, we evaluated the ability of dead-space ventilation measures to predict mortality in patients with ARDS. DATA SOURCES: MEDLINE, CENTRAL, and Google Scholar from inception to November 2022. STUDY SELECTION: Studies including adults with ARDS reporting a dead-space ventilation index and mortality. DATA EXTRACTION: Two reviewers independently identified eligible studies and extracted data. We calculated pooled effect estimates using a random effects model for both adjusted and unadjusted results. The quality and strength of evidence were assessed using the Quality in Prognostic Studies and Grading of Recommendations, Assessment, Development, and Evaluation, respectively. DATA SYNTHESIS: We included 28 studies in our review, 21 of which were included in our meta-analysis. All studies had a low risk of bias. A high pulmonary dead-space fraction was associated with increased mortality (odds ratio [OR], 3.52; 95% CI, 2.22-5.58; p < 0.001; I2 = 84%). After adjusting for other confounding variables, every 0.05 increase in pulmonary-dead space fraction was associated with an increased odds of death (OR, 1.23; 95% CI, 1.13-1.34; p < 0.001; I2 = 57%). A high ventilatory ratio was also associated with increased mortality (OR, 1.55; 95% CI, 1.33-1.80; p < 0.001; I2 = 48%). This association was independent of common confounding variables (OR, 1.33; 95% CI, 1.12-1.58; p = 0.001; I2 = 66%). CONCLUSIONS: Dead-space ventilation indices were independently associated with mortality in adults with ARDS. These indices could be incorporated into clinical trials and used to identify patients who could benefit from early institution of adjunctive therapies. The cut-offs identified in this study should be prospectively validated.

Ventilatory efficiency measured during sub-maximal cardiopulmonary exercise testing predicts postoperative outcomes following heart transplantation.

Cardiopulmonary exercise testing is commonly used to evaluate patients for heart transplantation. We assessed the utility of ventilatory efficiency (VE/VCO2 ) to predict perioperative outcomes following heart transplantation. We retrospectively reviewed all patients undergoing cardiopulmonary exercise testing prior to heart transplantation at our center. Spearman's coefficient showed a correlation between VE/VCO2 and ICU free days in the first 30-days post-transplant (R = -.37, p < .01). A VE /VCO2 cut-off >35 was associated with significantly lower median ICU-free days (23.0 vs. 27 days; p < .01) and a higher likelihood of postoperative morbidity (OR = 5.64, 95% CI = 1.75-18.16; p < .01). Multiple regression analysis controlling for peak oxygen consumption and right heart catheter parameters showed VE/VCO2 >35 is independently associated with lower ICU-free days (p < .01) and postoperative morbidity (p = .02). Peak oxygen consumption <15 mL/min/kg was not associated with higher ICU or hospital-free days. VE/VCO2 >35 independently predicts early postoperative morbidity in patients undergoing heart transplantation.

Exercise induced bronchodilation: a phenomenon more common, greater magnitude and more prolonged in older adults than in adolescents.

OBJECTIVE: There are few studies in clinically healthy subjects describing and quantifying exercise-induced bronchodilation (EIBd). This study aimed to describe and compare the magnitude and time course changes in post-exercise forced expired volume at the first second (FEV1) in healthy adolescents, younger adults, and older adults. METHODS: Adolescent (n = 73, aged 10-17 years), younger adult (n = 35, aged 18-25 years), and older adult (n = 25, aged 35-66 years) subjects with normal spirometry z-scores completed a maximal cardiopulmonary exercise test using the standardized exponential exercise test protocol on a cycle ergometer performed at stable temperature and humidity. Spirometry was performed pre-exercise and at 1-, 3-, 5-, and 10-minutes post-exercise to determine the percentage change in FEV1 compared to baseline. EIBd was defined as a ≥ 5% increase in post-exercise FEV1. RESULTS: Increases in FEV1 at one-minute post-exercise were observed in the adolescents (1.3%) and young adults (6.0%) with FEV1 returning to baseline after ten minutes. Compared to the adolescents, the older adults showed significantly greater and sustained increases in FEV1 at 1-, 3-, 5-, and 10-minutes post-exercise (6.4, 4.6, 4.7, and 3.8%, p < 0.05). At 1-minute post exercise a significantly greater proportion of younger adults (54%, p < 0.01) and older adults (64%, p < 0.01) demonstrated EIBd compared to the adolescent group (15%). CONCLUSION: Healthy older adults had a higher prevalence, greater magnitude and more prolonged EIBd compared to healthy adolescent and young adult subjects.

Cardiorespiratory responses to muscle metaboreflex activation in fibrosing interstitial lung disease.

NEW FINDINGS: What is the central question of this study? We determined whether sensory feedback from metabolically sensitive skeletal muscle afferents (metaboreflex) causes a greater ventilatory response and higher dyspnoea ratings in fibrosing interstitial lung disease (FILD). What is the main finding and its importance? Ventilatory responses and dyspnoea ratings during handgrip exercise and metaboreflex isolation were not different in FILD and control groups. Blood pressure and heart rate responses to handgrip were attenuated in FILD but not different to controls during metaboreflex isolation. These findings suggest that the muscle metaboreflex contribution to the respiratory response to exercise is not altered in FILD. ABSTRACT: Exercise limitation and dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD); however, the physiological mechanisms are poorly understood. In other respiratory diseases, there is evidence that an augmented muscle metaboreflex may be implicated. We hypothesized that metaboreflex activation in FILD would result in elevated ventilation and dyspnoea ratings compared to healthy controls, due to augmented muscle metaboreflex. Sixteen FILD patients (three women, 69±14 years; mean±SD) and 16 age-matched controls (four women, 67±7 years) were recruited. In a randomized cross-over design, participants completed two min of rhythmic handgrip followed by either (i) two min of post-exercise circulatory occlusion (PECO trial) to isolate muscle metaboreflex activation, or (ii) rested for four min (Control trial). Minute ventilation ( V̇E$\dot{V}_E$ ; pneumotachometer), dyspnoea ratings (0-10 Borg scale), mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were measured. V̇E$\dot{V}_E$ was higher in the FILD group at baseline and exercise increased V̇E$\dot{V}_E$ similarly in both groups. V̇E$\dot{V}_E$ remained elevated during PECO, but there was no between-group difference in the magnitude of this response (Δ V̇E$\dot{V}_E$ FILD 4.2 ± 2.5 L·min-1  vs. controls 3.6 ± 2.4 L·min-1 , P = 0.596). At the end of PECO, dyspnoea ratings in FILD were similar to controls (1.0 ± 1.3 units vs. 0.5 ± 1.1 units). Exercise increased MAP and HR (P < 0.05) in both groups; however, responses were lower in FILD. Collectively, these findings suggest that there is not an augmented effect of the muscle metaboreflex on breathing and dyspnoea in FILD, but haemodynamic responses to handgrip are reduced relative to controls.

Surgical treatment of non-small-cell lung cancer in octogenarians: a single-centre retrospective study.

Lung resection in patients aged ≥80 years is considered high risk and contributes to the low rates of resection in this population. This review of 79 octogenarians who underwent curative surgery for non-small-cell lung cancer demonstrated no intraoperative mortality, 30-day mortality of 1.3% and 12-month mortality of 10%. In this selected cohort of octogenarians, surgery resulted in acceptable short- to medium-term outcomes.

Inhaled corticosteroids for bronchiectasis.

BACKGROUND: Bronchiectasis is being increasingly diagnosed and recognised as an important contributor to chronic lung disease in both adults and children in high- and low-income countries. It is characterised by irreversible dilatation of airways and is generally associated with airway inflammation and chronic bacterial infection. Medical management largely aims to reduce morbidity by controlling the symptoms, reduce exacerbation frequency, improve quality of life and prevent the progression of bronchiectasis. This is an update of a review first published in 2000. OBJECTIVES: To evaluate the efficacy and safety of inhaled corticosteroids (ICS) in children and adults with stable state bronchiectasis, specifically to assess whether the use of ICS: (1) reduces the severity and frequency of acute respiratory exacerbations; or (2) affects long-term pulmonary function decline. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Register of trials, MEDLINE and Embase databases. We ran the latest literature search in June 2017. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing ICS with a placebo or no medication. We included children and adults with clinical or radiographic evidence of bronchiectasis, but excluded people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: We reviewed search results against predetermined criteria for inclusion. In this update, two independent review authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro forma. We analysed treatment as 'treatment received' and performed sensitivity analyses. MAIN RESULTS: The review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies.Due to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months).During stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV1) at the end of the study (mean difference (MD) -0.09, 95% confidence interval (CI) -0.26 to 0.09) and forced vital capacity (FVC) (MD 0.01 L, 95% CI -0.16 to 0.17) in adults on ICS (compared to no ICS). Similarly, we did not find any significant difference in the average exacerbation frequency (MD 0.09, 95% CI -0.61 to 0.79) or health-related quality of life (HRQoL) total scores in adults on ICS when compared with no ICS, though data available were limited. Based on a single non-placebo controlled study from which we could not extract clinical data, there was marginal, though statistically significant improvement in sputum volume and dyspnoea scores on ICS.The single study on long-term outcomes (over 6 months) that examined lung function and other clinical outcomes, showed no significant effect of ICS on any of the outcomes. We could not draw any conclusion on adverse effects due to limited available data.Despite the authors of all seven studies stating they were double-blind, we judged one study (in the short duration ICS) as having a high risk of bias based on blinding, attrition and reporting of outcomes. The GRADE quality of evidence was low for all outcomes (due to non-placebo controlled trial, indirectness and imprecision with small numbers of participants and studies). AUTHORS' CONCLUSIONS: This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.

An international, multicentre evaluation and description of Burkholderia pseudomallei infection in cystic fibrosis.

BACKGROUND: Several cases of Burkholderia pseudomallei infection in CF have been previously reported. We aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies. METHODS: We performed a literature search to identify all published cases of B. pseudomallei infection in CF. In addition we hand-searched respiratory journals, and contacted experts in infectious diseases and CF around the world. Supervising clinicians for identified cases were contacted and contemporaneous clinical data was requested. RESULTS: 25 culture-confirmed cases were identified. The median age at acquisition was 21 years, mean FEV1 % predicted was 60 %, and mean BMI was 19.5 kg/m(2). The location of acquisition was northern Australia or south-east Asia for most. 19 patients (76 %) developed chronic infection, which was usually associated with clinical decline. Successful eradication strategies included a minimum of two weeks of intravenous ceftazidime, followed by a consolidation phase with trimethoprim/sulfamethoxazole, and this resulted in a higher chance of success when instituted early. Three cases of lung transplantation have been recorded in the setting of chronic B. pseudomallei infection. CONCLUSION: Chronic carriage of B. pseudomallei in patients with CF appears common after infection, in contrast to the non-CF population. This is often associated with an accelerated clinical decline. Lung transplantation has been performed in select cases of chronic B. pseudomallei infection.

The relationships among dyspnoea, health-related quality of life and psychological factors in sarcoidosis.

BACKGROUND AND OBJECTIVES: Dyspnoea is a common symptom in sarcoidosis and is not predictably related to pulmonary function or radiology. A subjective symptom of dyspnoea is likely to be influenced by patient perception and experience. The aim of this study was to determine the prevalence and nature of dyspnoea in sarcoidosis and describe the relationship of dyspnoea to psychological factors and health-related quality of life (HRQL). METHODS: Fifty-six subjects (31 men, mean age 51 years) with sarcoidosis completed an HRQL measure, St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS) and Nijmegen questionnaire. The presence of symptoms of dyspnoea was noted and qualitative descriptors for dyspnoea were chosen at peak exercise. Resting pulmonary function was performed. RESULTS: Sixty-four per cent of the subjects reported dyspnoea. Those with symptoms were older, had a longer duration of disease and with lower forced expiratory volume in 1 s (FEV1 ) and FEV1 /forced vital capacity (FVC) (all P < 0.05). Symptoms of dyspnoea were associated with worse HRQL (P < 0.005) and higher scores on the Nijmegen questionnaire (P < 0.05). Anxiety was not associated with dyspnoea and only a trend to greater depression was observed (P = 0.066). In multivariate analysis, SGRQ and Nijmegen scores predicted dyspnoea independent of demographic factors and resting pulmonary function. CONCLUSION: Dyspnoea is common in sarcoidosis and is associated with worse HRQL irrespective of baseline pulmonary function. Hyperventilation appears to be a factor contributing to dyspnoea and the Nijmegen questionnaire may be helpful in assessing dyspnoea and hyperventilation in sarcoidosis patients.

Comparison of the modified shuttle walk test and cardiopulmonary exercise test in sarcoidosis.

BACKGROUND AND OBJECTIVE: Dyspnoea and exercise intolerance are common in sarcoidosis and are often poorly correlated with resting lung function. Measurement of peak exercise capacity is likely to be helpful in assessing and monitoring disease. The aim of this study was to compare the modified shuttle walk test (MSWT) to cardiopulmonary exercise test (CPET) as a measure of peak exercise capacity in sarcoidosis. METHODS: Thirty-three (17 male, mean age 48 years) patients with sarcoidosis completed a standardized exponential exercise protocol cycle ergometer CPET and a single corridor MSWT in random order. RESULTS: Subjects has a mean forced expiratory volume in 1 s (FEV1) 2.4 L (75.7%predicted), forced vital capacity (FVC) 3.43 L (88.7%predicted) and diffusing capacity for carbon monoxide (DLCO) 20.3 mL/min/mm Hg (71.4%predicted). There was a strong correlation between MSWT distance and peak oxygen uptake (VO2) during CPET (r = 0.87; P < 0.0001), and between maximum heart rate during MSWT and CPET (r = 0.82; P < 0.0001). There was a moderate correlation between FEV1 , FVC and DLCO with MSWT distance (r = 0.55, r = 0.61, r = 0.61, respectively; all P < 0.001) and with peak VO2 (r = 0.62, r = 0.63, r = 0.62, respectively; all P < 0.0001). CONCLUSIONS: Peak VO2 achieved during CPET strongly correlated with MSWT distance. MSWT is a measure of peak exercise capacity in sarcoidosis that does not require equipment and can be readily available in the clinic.

Respiratory effects of insulin sensitisation with metformin: a prospective observational study.

The mechanism for the association between diabetes mellitus and lung function impairment is unknown, as are any respiratory effects of antidiabetic agents. We aimed to assess whether treatment with metformin, an oral insulin-sensitising agent, improved lung function or symptoms in individuals with COPD and glucose intolerance. A prospective open-label observational study was conducted. Participants with moderate or severe COPD, BMI > 25 kg/m(2), and type 2 diabetes mellitus or impaired glucose tolerance took metformin twice daily for 6 months. Clinical outcomes included St George's Respiratory Questionnaire (SGRQ), transition dyspnoea index, and incremental shuttle walk test. Physiological outcomes including pulmonary function tests, exhaled nitric oxide, respiratory mouth pressures and handgrip strength. In total, 17 participants completed the study. SGRQ score improved by a median of 5 points, and TDI scores improved by 2 points. Inspiratory mouth pressures increased by 7.5 cmH2O. There were trends to improvements in hyperinflation, gas trapping and shuttle walk distance. Spirometry and exhaled nitric oxide were unchanged. In this proof-of-concept study, metformin was associated with improved dyspnoea and health status in COPD, possibly related to increased inspiratory muscle strength. These and other endpoints should be examined in a definitive study.

Chronic obstructive pulmonary disease in non-smokers: a case-comparison study.

BACKGROUND: COPD is often regarded as a smoker's disease. In fact, up to 50% of COPD could be attributable to other causes. Relatively little is known about COPD among nonsmokers, and this group is usually excluded from studies of COPD. METHODS: In this cross-sectional case-comparison study, smokers and nonsmokers aged over 45 with COPD (post-bronchodilator FEV1 ≤ 70% predicted, FEV1/FVC ratio < 0.7) were recruited from specialist outpatient clinics and from primary care. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, formal lung function testing and high resolution CT. RESULTS: 48 nonsmokers and 45 smokers participated. Asthma was nearly universal among nonsmokers and was the commonest identifiable cause of COPD in that group. Nonsmokers also exhibited a high prevalence of objective eosinophilic inflammation (raised ENO and eosinophil counts, positive skinprick tests). Smokers had more severe airflow obstruction, but respiratory symptom prevalences were similar between groups. Nonsmokers reported greater lifetime burdens of respiratory disease. Nonsmokers' HRCT results showed functional small airways disease, with no significant emphysema in any subject. Previously undiagnosed bronchiectasis was common in both groups (31% and 42%). CONCLUSIONS: Asthma is a very common cause of COPD among nonsmokers. Radiological bronchiectasis is common in COPD; the clinical significance of this finding is unclear.

Closure of a broncho-pleural fistula using an atrial septal defect occluder.

Broncho-pleural fistulae (BPF) are recognised as a rare complication following pneumonectomy. We describe a patient, who after failing conservative treatment, underwent closure of a persistent fistula with an atrial septal defect (ASD) occluder. Additionally we review the literature regarding management of BPF and the emerging role of cardiac defect closure devices as a possible treatment option.

Clinical utility of the Borg dyspnoea score in 6-minute walk tests in interstitial lung disease: A systematic review.

BACKGROUND: Exertional dyspnoea, a cardinal symptom in interstitial lung disease (ILD), can be objectively measured during a 6-min walk test (6MWT) using the Borg Dyspnoea Score (BDS). However, the clinical utility of this measurement is unclear. The purpose of this systematic review was to determine the association between 6MWT BDS and prognosis (mortality and lung transplantation), other 6MWT variables and measures of pulmonary function. METHODS: MEDLINE, EMBASE, Cochrane and SCOPUS databases were used to identify studies reporting an association between post-6MWT BDS and the relevant outcomes in adults with ILD. Language was limited to English. Study quality was assessed using the Quality in Prognosis Study risk of bias tool. A narrative synthesis for each outcome was performed. RESULTS: Ten full-text studies (n = 518) were included. Four studies had high overall risk of bias. Two studies (n = 127) reported prognosis and both found that higher 6MWT BDS was associated with increased all-cause mortality. However, the certainty of evidence was very low due to study design and likely publication bias. Higher post-6MWT BDS may be associated with shorter, or no effect on 6MWD; and lower pulmonary function. There was insufficient evidence that BDS correlated with 6MWT oxygen saturation. CONCLUSIONS: Post-6MWT BDS has a potential role as a predictor of all-cause mortality in ILD, 6MWD and lower pulmonary function. Larger studies designed to confirm these relationships and assess the independent association between the 6MWT BDS and clinical outcomes are required.

Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery. METHODS: Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation-after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study. RESULTS: DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs -0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events. CONCLUSIONS: Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population.

Fixed airflow obstruction among nonsmokers with asthma:a case-comparison study.

BACKGROUND: Airflow obstruction in asthma is usually reversible, but fixed obstruction develops in some individuals. Little is known about risk factors for development of fixed airflow obstruction in nonsmokers with asthma. METHODS: This case-comparison study recruited nonsmokers aged over 45 years with physician-diagnosed asthma from specialist outpatient clinics and primary care. Two age-matched groups were recruited on the basis of spirometry: anobstructed group (post-bronchodilator FEV(1) ≤ 70% predicted, FEV1/FVC ratio < lower limit of normal) and a control group with normal lung function. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, and formal lung function testing. RESULTS: Thirty-four obstructed subjects and 40 controls participated in the study. Obstructed subjects exhibited greater evidence of systemic inflammation, abnormal glucose homeostasis, and central obesity than controls. Obstructed subjects reported longer duration of asthma, and childhood respiratory infection was commoner in that group. Metabolic syndrome prevalence was similar between groups, but several features of insulin resistance were associated with reduced FEV(1). Cough and sputum were common among controls. CONCLUSIONS: Risk of fixed airflow obstruction may correlate with lifetime asthma duration. Individuals with coexisting asthma and fixed airflow obstruction have heightened systemic inflammation. A variety of chronic respiratory symptoms are common among "healthy" nonsmokers with asthma.

Influence of mediterranean diet on asthma symptoms, lung function, and systemic inflammation: a randomized controlled trial.

OBJECTIVE: The rapidly increasing prevalence of asthma in developed countries suggests an environmental cause. The benefits of Mediterranean diet (MD) in cardiovascular disease have been tentatively attributed to its anti-inflammatory properties. Asthma is an inflammatory disease and MD is associated with reduced asthma risk in epidemiological studies, but there are no reported interventional studies of MD in asthma. METHODS: In this 12-week open-label randomized trial, 38 adults with symptomatic asthma were allocated to high-intervention (HI), low-intervention (LI), and control groups. The first two groups were encouraged to adopt an MD and received multiple consultation sessions with a nutritionist, written advice, and vouchers for the purchase of appropriate foods. Food frequency questionnaires, asthma control questionnaires, asthma-related quality of life questionnaires (AQLQs), and spirometry were completed at the beginning and at the end of the study. RESULTS: The MDt score increased in the HI group (p < .001), indicating successful alteration of dietary behavior. Statistically, nonsignificant improvements were seen in spirometry and several AQLQ subdomains in the two intervention groups. No changes were seen in the asthma control or in inflammatory markers. CONCLUSIONS: The trial intervention has successfully altered the dietary behavior among adults with asthma. Small but consistent improvements were seen in quality of life and spirometry among the intervention group. The use of the MD to treat asthma is feasible and warrants evaluation in a larger study, powered to examine clinical endpoints.

The prevalence and predictors of airway hyperresponsiveness in sarcoidosis.

BACKGROUND AND OBJECTIVE: Obstructive airflow limitation is the most common physiological impairment in sarcoidosis. This study determined the prevalence of airway hyperresponsiveness (AHR) in sarcoidosis, the correlation between responses to direct (using histamine) and indirect (using hypertonic saline) bronchial challenge, and the clinical, physiological and radiological predictors of AHR. METHODS: Subjects with sarcoidosis and a baseline forced expiratory volume in 1 s (FEV(1)) >35% predicted underwent hypertonic and histamine challenge, lung function testing and high resolution computed tomography (HRCT) of the chest. AHR was defined as a 15% fall in FEV(1) to hypertonic saline and a 20% fall in FEV(1) to histamine. RESULTS: The 52 subjects had well-preserved lung function (FEV(1) = 2.8 ± 0.7 L, 87% predicted). AHR was detected in 5/47 (11%) to hypertonic saline and 19/43 (44%) to histamine challenge. On univariate analysis, response to histamine challenge was predicted by conglomerate fibrosis (P = 0.02) and reticular pattern (P = 0.03) on HRCT. The baseline % predicted forced expiratory volume in 1 s was significantly inversely associated with AHR on univariate (P = 0.004) and multivariate analysis (P = 0.01) when adjusted by HRCT patterns. CONCLUSIONS: The higher prevalence of AHR using histamine challenge than hypertonic saline challenge and the association with baseline % predicted FEV(1) suggest that the AHR in sarcoidosis may reflect the consequences of airway remodelling following inflammation.