Katherine L. Vandemheen

Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis

Background Despite advances in treatment of cystic fibrosis (CF), pulmonary exacerbations remain common. The aim of this study was to determine if frequent pulmonary exacerbations are associated with greater declines in lung function, or an accelerated time to death or lung transplantation in adults with CF. Methods A 3-year prospective cohort study was conducted on 446 adult patients with CF from Ontario, Canada who could spontaneously produce sputum. Patients enrolled from 2005 to 2008 and were stratified into groups based upon their exacerbation rates over the 3 year study: <1 exacerbation/year (n=140), 1–2 exacerbations/year (n=160) and >2 exacerbations/year (n=146). Exacerbations were defined as acute/subacute worsening of respiratory symptoms severe enough to warrant oral or intravenous antibiotics. Patient-related factors associated with frequent exacerbations were determined, and clinical outcomes were compared among the three exacerbation groups. Results Patients with frequent exacerbations were more likely to be female, diabetic and have poorer baseline lung function. Patients with >2 exacerbations/year had an increased risk of experiencing a 5% decline from baseline forced expiratory volume in 1 s (FEV1); unadjusted HR 1.47 (95% CI 1.07 to 2.01, p=0.02), adjusted HR 1.55 (95% CI 1.10 to 2.18, p=0.01) compared with patients with <1 exacerbation/year. Patients with >2 exacerbations/year also had an increased risk of lung transplant or death over the 3 year study; unadjusted HR 12.74 (95% CI 3.92 to 41.36, p<0.0001), adjusted HR 4.05 (95% CI 1.15 to 14.28, p=0.03). Conclusions Patients with CF with frequent exacerbations appear to experience an accelerated decline in lung function, and they have an increased 3 year risk of death or lung transplant.

Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma.

Importance Although asthma is a chronic disease, the expected rate of spontaneous remissions of adult asthma and the stability of diagnosis are unknown. Objective To determine whether a diagnosis of current asthma could be ruled out and asthma medications safely stopped in randomly selected adults with physician-diagnosed asthma. Design, Setting, and Participants A prospective, multicenter cohort study was conducted in 10 Canadian cities from January 2012 to February 2016. Random digit dialing was used to recruit adult participants who reported a history of physician-diagnosed asthma established within the past 5 years. Participants using long-term oral steroids and participants unable to be tested using spirometry were excluded. Information from the diagnosing physician was obtained to determine how the diagnosis of asthma was originally made in the community. Of 1026 potential participants who fulfilled eligibility criteria during telephone screening, 701 (68.3%) agreed to enter into the study. All participants were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over 4 study visits. Participants in whom a diagnosis of current asthma was ultimately ruled out were followed up clinically with repeated bronchial challenge tests over 1 year. Exposure Physician-diagnosed asthma established within the past 5 years. Main Outcomes and Measures The primary outcome was the proportion of participants in whom a diagnosis of current asthma was ruled out, defined as participants who exhibited no evidence of acute worsening of asthma symptoms, reversible airflow obstruction, or bronchial hyperresponsiveness after having all asthma medications tapered off and after a study pulmonologist established an alternative diagnosis. Secondary outcomes included the proportion with asthma ruled out after 12 months and the proportion who underwent an appropriate initial diagnostic workup for asthma in the community. Results Of 701 participants (mean [SD] age, 51 [16] years; 467 women [67%]), 613 completed the study and could be conclusively evaluated for a diagnosis of current asthma. Current asthma was ruled out in 203 of 613 study participants (33.1%; 95% CI, 29.4%-36.8%). Twelve participants (2.0%) were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community. After an additional 12 months of follow-up, 181 participants (29.5%; 95% CI, 25.9%-33.1%) continued to exhibit no clinical or laboratory evidence of asthma. Participants in whom current asthma was ruled out, compared with those in whom it was confirmed, were less likely to have undergone testing for airflow limitation in the community at the time of initial diagnosis (43.8% vs 55.6%, respectively; absolute difference, 11.8%; 95% CI, 2.1%-21.5%). Conclusions and Relevance Among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. In patients such as these, reassessing the asthma diagnosis may be warranted.

A Comparison of Obese and Nonobese People With Asthma Exploring an Asthma-Obesity Interaction

OBJECTIVE The objectives of our study were to compare patient characteristics and severity of disease in obese and normal-weight-confirmed people with asthma and to explore reasons for misdiagnosis of asthma, including potential interactions with obesity. METHODS We randomly selected patients with physician-diagnosed asthma from eight Canadian cities. Asthma diagnosis was confirmed via a sequential lung function testing algorithm. Logistic analysis was conducted to compare obese and normal-weight-confirmed people with asthma and to assess characteristics associated with misdiagnosis of asthma. Interaction with obesity was investigated. RESULTS Complete assessments were obtained on 496 subjects who reported physician-diagnosed asthma (242 obese and 254 normal-weight subjects); 346 had asthma confirmed with sequential lung testing, and in 150 subjects a diagnosis of asthma was ruled out. Obese subjects with asthma were significantly more likely to be men, have a history of hypertension and gastroesophageal reflux disease, and have a lower FEV(1) compared with normal-weight subjects with asthma. Older subjects, men, and subjects with higher FEV(1) were more likely to have received misdiagnoses of asthma. Obesity was not an independent predictor of misdiagnosis, however there was an interaction between obesity and urgent visits for respiratory symptoms. The odds ratio for receiving a misdiagnosis of asthma for obese individuals as compared with normal-weight individuals was 4.08 (95% CI, 1.23-13.5) for those with urgent visits in the past 12 months. CONCLUSIONS Obese people with asthma have lower lung function and more comorbidities compared with normal-weight people with asthma. Obese individuals who make urgent visits for respiratory symptoms are more likely to receive a misdiagnosis of asthma.

Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD.

Background: Little is known about the combination of different medications in chronic obstructive pulmonary disease (COPD). This study determined the cost effectiveness of adding salmeterol (S) or fluticasone/salmeterol (FS) to tiotropium (T) for COPD. Methods: This concurrent, prospective, economic analysis was based on costs and health outcomes from a 52 week randomised study comparing: (1) T 18 µg once daily + placebo twice daily (TP group); (2) T 18 µg once daily + S 25 µg/puff, 2 puffs twice daily (TS group); and (3) T 18 µg once daily + FS 250/25 µg/puff, 2 puffs twice daily (TFS group). The incremental cost effectiveness ratios (ICERs) were defined as incremental cost per exacerbation avoided, and per additional quality adjusted life year (QALY) between treatments. A combination of imputation and bootstrapping was used to quantify uncertainty, and extensive sensitivity analyses were performed. Results: The average patient in the TP group generated CAN

TNFα antagonists for acute exacerbations of COPD: a randomised double-blind controlled trial

2678 in direct medical costs compared with

Treatment of Aspergillus fumigatus in Patients with Cystic Fibrosis: A Randomized, Placebo-Controlled Pilot Study

2801 (TS group) and

Effects of Weight Loss on Airway Responsiveness in Obese Adults With Asthma: Does Weight Loss Lead to Reversibility of Asthma?

4042 (TFS group). The TS strategy was dominated by TP and TFS. Compared with TP, the TFS strategy resulted in ICERs of

(Correcting) misdiagnoses of asthma: a cost effectiveness analysis

6510 per exacerbation avoided, and

Effect of infection with transmissible strains of Pseudomonas aeruginosa on lung transplantation outcomes in patients with cystic fibrosis

243 180 per QALY gained. In those with severe COPD, TS resulted in equal exacerbation rates and slightly lower costs compared with TP. Conclusions: TFS had significantly better quality of life and fewer hospitalisations than patients treated with TP but these improvements in health outcomes were associated with increased costs. Neither TFS nor TS are economically attractive alternatives compared with monotherapy with T.

Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations

Background The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone. Methods We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patients forced expiratory volume in 1 s (FEV1) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life. Results At 14 days the mean±SE change in FEV1 from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI −10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08). Conclusions Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%. Clinical Trials gov number NCT 00789997.