A retrospective study of crossover ambulatory oxygen walk testing in patients with fibrotic lung disease.

BACKGROUND: Fibrotic interstitial lung disease (ILD) comprises a group of lung conditions that are often progressive, debilitating, and life-shortening. Ambulatory oxygen therapy (AOT) is regularly prescribed to manage symptoms in patients with fibrotic ILD. In our institution, the decision to prescribe portable oxygen is made on the basis of oxygen improving exercise capacity, measured with the single-blinded, crossover ambulatory oxygen walk test (AOWT). This study aimed to investigate the characteristics and survival rates of patients with fibrotic ILD who have either positive or negative results on the AOWT. METHODS: This retrospective cohort study compared the data from 99 patients with fibrotic ILD who underwent the AOWT. These patients were classified into two groups based on whether they showed improvement in the AOWT with supplemental oxygen (positive group) or no improvement (negative group). Patient demographics for both groups were compared to determine any significant differences. A multivariate Cox proportional hazards model was used to analyze the survival rates of the two groups. RESULTS: Out of the 99 patients, 71 were in the positive group. We compared the measured characteristics between the positive and negative groups and found no significant difference, wherein the adjusted hazard ratio was 1.33 (95% confidence interval 0.69-2.60, P = 0.40). CONCLUSIONS: The AOWT can be used to rationalize AOT, but there was no significant difference in baseline characteristics or survival rates between patients whose performance was improved or not in the AOWT.

Early Exacerbation Relapse is Increased in Patients with Asthma and Bronchiectasis (a Post hoc Analysis).

PURPOSE: Asthma is a common comorbidity in patients with bronchiectasis and has been shown to increase the risk of bronchiectasis exacerbations. This paper explores the impact of comorbid asthma on patients receiving intravenous antibiotic treatment for bronchiectasis exacerbations. METHODS: This was a post hoc analysis of the Meropenem randomised controlled trial of 90 patients that had intravenous antibiotic treatment for bronchiectasis exacerbations. The participants were split into two groups: group 1 (asthma and bronchiectasis) and group 2 (bronchiectasis). The authors assessed response to treatment and time to next exacerbation. RESULTS: There were 38 participants in group 1 and 34 participants in group 2. The groups were found to be comparable in terms of age, sex, and bronchiectasis severity (median (95% CI) group 1 and then group 2 data): age 64.0(59.3, 68.6) and 63.6(57.9, 69.4) years old, p = 0.8; 57.9% and 64.7% female, p = 0.6; Bronchiectasis Severity Index 11.1(9.8, 12.4) and 10.1(8.2, 12.0), p = 0.3. There was a similar response to treatment between the groups, but group 1 were found to relapse early by day 14, 31.6% in group 1 and 11.8% in group 2, p = 0.03. In the Cox proportional hazards model, asthma was the only independent risk factor for early relapse by day 14 (odds ratio (95% CI) 3.16 (1.02-9.79), p = 0.047). CONCLUSION: The clinical response to treatment was similar but patients with coexisting asthma were at increased risk of early relapse within 14 days of stopping intravenous antibiotic therapy. CLINICAL TRIAL REGISTRATION: NCT02047773.

Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial.

BACKGROUND: There is a lack of evidence to guide the duration of intravenous antibiotics for bronchiectasis exacerbations. AIMS: The aim of this study was to assess whether it is feasible, based on bacterial load, to shorten intravenous antibiotics during exacerbations and whether 14 days of treatment is superior. METHODS: We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups: to receive antibiotics for 14 days (14-day group) or to have a shorter duration of treatment based on bacterial load (bacterial load-guided group (BLGG)). Bacterial load was checked on days 0, 7, 10, 14 and 21. If the bacterial load was <106 CFU·mL-1 on day 7 or day 10 in the BLGG, antibiotics were stopped the following day. RESULTS: A total of 47 participants were in the 14-day group and 43 were in the BLGG. 88% of participants in the BLGG were able to stop antibiotics by day 8 and potentially 81% of participants in the 14-day group could have stopped antibiotics at day 8. There was a nonsignificant trend for increased clinical improvement by day 21 in the 14-day group compared to the BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5 days (12.5-60 days) in the 14-day group and 60 days (18-110 days) in the in BLGG (p=0.0034). In a Cox proportional hazard model, participants in the 14-day group were more likely to experience exacerbations (HR 1.80, 95% CI 1.16-2.80, p=0.009) than those in the BLGG, and those with mild bronchiectasis were less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359, 95% CI 0.13-0.99, p=0.048). CONCLUSIONS: Bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a nonsignificant trend for increased clinical improvement by day 21 with 14 days of antibiotics compared with bacterial load-guided therapy but paradoxically there was a prolonged time to next exacerbation in the BLGG.

Validation of the Incremental Shuttle Walk Test as a Clinical End Point in Bronchiectasis.

BACKGROUND: A validated clinical end point is needed to assess response to therapies in bronchiectasis. OBJECTIVES: The goal of this study was to assess the reliability, validity, and responsiveness of the incremental shuttle walk test (ISWT) as a clinical end point in bronchiectasis. METHODS: In clinically stable patients (n = 30), the ISWT was performed twice, 6 months apart. Correlation between the St. George's Respiratory Questionnaire (SGRQ) and the ISWT (n = 94) was performed. The 1-year gentamicin study was reanalyzed to assess the area under the curve (percent change of ISWT with a ≥ 4 unit improvement in total SGRQ). ISWT was performed prior to and following 14 days of antibiotics for an exacerbation (94 oral courses and 30 IV courses, n = 124) and reanalysis of the 1-year gentamicin study (n = 57). RESULTS: The ISWT did not significantly change over 6 months while clinically stable. The ISWT correlated inversely with the SGRQ (rs = -0.60; P < .0001), Bronchiectasis Severity Index score (rs = -0.44; P < .0001), and sedentary time (rs = -0.48; P = .0007) but correlated with physical activity (rs = 0.42; P = .004). The area under the curve for percent change in ISWT with ≥ 4 unit improvement in SGRQ was 0.79 (95% CI, 0.66-0.91; P = .001). A threshold of 5% improvement in the ISWT had a 92% sensitivity but 50% specificity, and from the responsiveness studies would capture 73% of all patients. CONCLUSIONS: This study confirmed the ISWT to be reliable, valid, and responsive to change in patients with bronchiectasis. The authors propose that a minimum clinically important difference of 5% improvement in the ISWT would be a useful objective end point to assess therapies in bronchiectasis.

The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

OBJECTIVES: The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. METHODS: The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. RESULTS: A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV1, sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV1, 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. CONCLUSIONS: A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis.

Inhaled or nebulised ciprofloxacin for the maintenance treatment of bronchiectasis.

INTRODUCTION: Inhaled or nebulised antibiotics are a major topic of ongoing research interest in reducing exacerbations in bronchiectasis. There are no licenced inhaled or nebulised antibiotics currently in bronchiectasis. Areas covered: Inhaled or nebulised ciprofloxacin as a long-term treatment in bronchiectasis. Expert opinion: Results from the Phase III ongoing trials on inhaled or nebulised ciprofloxacin will be key for the outcome of the drugs but additionally, cost-effectiveness and longer-term studies will be necessary to determine the viability of the drug. Head to head studies are needed to decide on the optimum inhaled or nebulised antibiotic and their place with or without long term macrolide therapy. It is also important to determine what treatment is viable for acute exacerbations due to P. aeruginosa. Ciprofloxacin is the only currently available oral agent for exacerbations due to P. aeruginosa. The concern is that using inhaled or nebulised ciprofloxacin will prevent the use and efficacy of its oral equivalent, by developing resistance.