Pallavi Bedi

A prospective cohort study of the use of domiciliary intravenous antibiotics in bronchiectasis

Background:We introduced domiciliary intravenous (IV) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment.Aim:To assess the efficacy and safety of domiciliary IV antibiotic therapy in patients with non-cystic fibrosis bronchiectasis.Methods:In this prospective study conducted over 5 years, we assessed patients’ eligibility for receiving domiciliary treatment. All patients received 14 days of IV antibiotic therapy and were monitored at baseline/day 7/day 14. We assessed the treatment outcome, morbidity, mortality and 30-day readmission rates.Results:A total of 116 patients received 196 courses of IV antibiotics. Eighty courses were delivered as inpatient treatment, 32 as early supported discharge (ESD) and 84 as domiciliary therapy. There was significant clinical and quality of life improvement in all groups, with resolution of infection in 76% in the inpatient group, 80% in the ESD group and 80% in the domiciliary group. Morbidity was recorded in 13.8% in the inpatient group, 9.4% in the ESD group and 14.2% in the domiciliary IV group. No mortality was recorded in either group. Thirty-day readmission rates were 13.8% in the inpatient group, 12.5% in the ESD group and 14.2% in the domiciliary group. Total bed days saved was 1443.Conclusion:Domiciliary IV antibiotic therapy in bronchiectasis is clinically effective and was safe in our cohort of patients.

Bronchiectasis Severity Is an Independent Risk Factor for Vascular Disease in a Bronchiectasis Cohort

Background: Interest in the association of vascular disease with COPD and pneumonia has increased, but there is a lack of research in this area with patients with bronchiectasis. Methods: A retrospective study of 400 patients attending a specialist bronchiectasis clinic in NHS Lothian (Edinburgh, UK) between May 2013 and September 2014 was conducted. The study assessed the prevalence of vascular disease (ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and atrial fibrillation). Using multivariable models, independent risk factors were identified for vascular disease that developed following the diagnosis of bronchiectasis. Results: The study included 400 patients. There was preexisting vascular disease (ie, before the diagnosis of bronchiectasis) in 44 patients (11%), and vascular disease occurred after the diagnosis of bronchiectasis after a mean of 9.4 years (95% CI, 6.0–12.8 years) in 45 patients (11%). Independent factors associated with all‐cause vascular disease after the diagnosis of bronchiectasis included male sex, hypertension, receiving long‐term statin therapy, and having moderate‐severity bronchiectasis or worse. Conclusions: In conclusion, bronchiectasis severity is independently associated with the development of vascular disease after the diagnosis of bronchiectasis. Future studies addressing the impact of primary and secondary prevention are warranted.

A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study

Background There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. Methods Thirty‐two patients chronically infected with P aeruginosa were recruited in this double‐blind cross‐over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. Results Twenty‐seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, –0.57‐4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (–5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C‐reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 &mgr;M reduced formyl‐methionyl‐leucyl phenylalanine‐induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. Conclusions We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. Trial Registry ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov

The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation. A case-crossover analysis

In bronchiectasis, exacerbations are believed to be triggered by infectious agents, but often no pathogen can be identified. We hypothesised that acute air pollution exposure may be associated with bronchiectasis exacerbations. We combined a case-crossover design with distributed lag models in an observational record linkage study. Patients were recruited from a specialist bronchiectasis clinic at Ninewells Hospital, Dundee, UK. We recruited 432 patients with clinically confirmed bronchiectasis, as diagnosed by high-resolution computed tomography. After excluding days with missing air pollution data, the final model for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) was based on 6741 exacerbations from 430 patients and for nitrogen dioxide (NO2) it included 6248 exacerbations from 426 patients. For each 10 µg·m−³ increase in PM10 and NO2, the risk of having an exacerbation that same day increased significantly by 4.5% (95% CI 0.9–8.3) and 3.2% (95% CI 0.7–5.8) respectively. The overall (lag zero to four) increase in risk of exacerbation for a 10 μg·m−3 increase in air pollutant concentration was 11.2% (95% CI 6.0–16.8) for PM10 and 4.7% (95% CI 0.1–9.5) for NO2. Subanalysis showed higher relative risks during spring (PM10 1.198 (95% CI 1.102–1.303), NO2 1.146 (95% CI 1.035–1.268)) and summer (PM10 2.142 (95% CI 1.785–2.570), NO2 1.352 (95% CI 1.140–1.602)) when outdoor air pollution exposure would be expected to be highest. In conclusion, acute air pollution fluctuations are associated with increased exacerbation risk in bronchiectasis. Acute air pollution fluctuations are associated with increased exacerbation risk in patients with bronchiectasis http://ow.ly/ehiN30khUOJ

Blood Neutrophils are Reprogrammed in Bronchiectasis.

Rationale: Excessive neutrophilic airway inflammation is the central feature of bronchiectasis, but little is known about neutrophils in bronchiectasis. Objectives: To assess blood neutrophil phenotype in patients with bronchiectasis while stable and during exacerbations. Methods: In the clinically stable arm of this study, there were eight healthy volunteers, eight patients with mild bronchiectasis, and eight patients with severe bronchiectasis. In addition, six patients with severe bronchiectasis were compared with six patients with community‐acquired pneumonia at the start and end of an exacerbation. We assessed neutrophils for spontaneous apoptosis, cell surface marker expression, degranulation, reactive oxygen species generation, phagocytosis, and killing of Pseudomonas aeruginosa (PAO1). In addition, blood neutrophil function was compared with airway neutrophil function in bronchiectasis. Measurements and Main Results: In stable bronchiectasis, compared with healthy volunteers, blood neutrophils had significantly prolonged viability, delayed apoptosis, increased CD62L shedding, upregulated CD11b expression, increased myeloperoxidase release, and impaired neutrophil phagocytosis and killing of PAO1. Bronchiectatic airway neutrophils had significantly lower bacterial phagocytosis and killing than their matched autologous blood neutrophils. Both blood and airway neutrophil phagocytosis and killing were impaired at the start of an exacerbation and improved following antibiotic treatment. In pneumonia, there was a significant improvement in phagocytosis and killing after treatment with antibiotics. During infections, there was no difference in phagocytosis, but there was significantly increased bacterial killing at the start and end of infection in pneumonia compared with bronchiectasis exacerbations. Conclusions: In bronchiectasis stable state, peripheral blood neutrophils are reprogrammed and have prolonged survival. This impairs their functional ability of bacterial phagocytosis and killing, thereby perpetuating the vicious circle in bronchiectasis.

Optimum Condition for Storage of Sputum from Patients with Bronchiectasis Infected with Haemophilus influenzae

Background: The optimum storage condition is not known for the isolation of H. influenzae in bronchiectasis patient sputum samples, the most common pathogen among bronchiectasis patients. The aim of the study was to assess the optimum sputum storage conditions for the isolation of Haemophilus influenzae from microbiological culture in patients with bronchiectasis. Method and findings: 20 stable bronchiectasis patients were recruited. The first three patients were used to assess reproducibility. 11 patient sputum samples were then collected and then stored for 2, 4, 6, 24 and 48 hours at room temperature and for 24 and 48 hours at 4°C, -20°C or -70°C before processing. The final 6 patient sputum samples were stored in 25% glycerol, 50% skimmed milk and neat at 4°C, -20°C and -70°C for 7 days before processing. Bacteria were identified and median log10 bacterial density (c.f.u./ml-1) and viable rates were calculated. There was good reproducibility with the coefficient of variation varying between 2-9%. The median baseline density of H. influenzae at room temperature was 1.2×108 c.f.u. ml-1. There was no significant difference in the density of H. influenzae cultured from the samples stored at room temperature and 4°C for any of the time points up to 48 h (room temperature: 48 h, 1.0×108 c.f.u. ml-1 and at 4°C: 48 h, 6.5×107 c.f.u. ml-1). Viable rates were the highest in samples left at room temperature for 48 h (81%). After 7 days of storage, only the sample stored at -70°C in glycerol (5.2×107 c.f.u. ml-1) showed no significant difference in the density of H. influenzae compared to processing right after collection (1.2×108 c.f.u. ml-1) and viable rates of 91%. Conclusion: The optimum conditions for sputum storage and processing for the isolation of H. influenzae from bronchiectasis patients are the storage at room temperature for up to 48 h and storage at -70°C in glycerol for up to 7 days.Introduction: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be up-regulated in various inflammatory diseases as well as in periodontal disease. The important role of E-cadherin against bacterial invasion has already been established in the junctional epithelium. This study aimed to evaluate the potential value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and E-cadherin as salivary diagnostic markers in patients with progressive chronic periodontitis. Material and method: A total of 79 subjects 41 females and 38 males, divided into 4 groups: healthy group (HG), early generalized chronic periodontitis group (EGP), moderate generalized chronic periodontitis group (MGP) and advanced generalized chronic periodontitis group (AGP), were included in the study. Enzymelinked immunosorbent assay (ELISA) test was used for quantification of sTREM-1 and E-cadherin in the saliva samples. Clinical and periodontal parameters were recorded and statistical analysis, using SPSS version 25.0, was performed. Results: Elevated salivary sTREM-1 levels were evident in EGP, MGP and AGP compared to the HG. Statistically significant differences in sTREM-1 concentrations were found between HG and AGP. Salivary E-cadherin was found to be upregulated during the progression of periodontal disease and statistically significant differences were found between HG and MPG. Conclusion: Salivary sTREM-1 may be considered a new biomarker in chronic periodontitis progression. E-cadherin, although detected, does not seem to have diagnostic value at salivary level in chronic adult periodontitis.

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. Georges 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.

Original Research: BronchiectasisA Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study

Background There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. Methods Thirty‐two patients chronically infected with P aeruginosa were recruited in this double‐blind cross‐over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. Results Twenty‐seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, –0.57‐4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (–5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C‐reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 &mgr;M reduced formyl‐methionyl‐leucyl phenylalanine‐induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. Conclusions We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. Trial Registry ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov

A randomised control trial of atorvastatin in bronchiectasis patients infected with Pseudomonas aeruginosa- a proof of concept study

Background There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. Methods Thirty‐two patients chronically infected with P aeruginosa were recruited in this double‐blind cross‐over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. Results Twenty‐seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, –0.57‐4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (–5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C‐reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 &mgr;M reduced formyl‐methionyl‐leucyl phenylalanine‐induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. Conclusions We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. Trial Registry ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov