Treatment Of Non-cystic Fibrosis Bronchiectasis Research Articles

Cathepsin C: structure, function, and pharmacological targeting

Cathepsin C is a papain-like cysteine peptidase known primarily for its involvement in the activation of serine peptidases in neutrophils and other immune cells. Its critical role in this process qualifies cathepsin C as a target for the treatment of inflammatory diseases, and its most advanced inhibitor, brensocatib (Insmed), is currently in phase 3 clinical trials for the treatment of non-cystic fibrosis bronchiectasis. Beyond neutrophils, its importance is highlighted by loss-of-function mutations that cause the recessively inherited Papillon-Lefèvre syndrome. At the molecular level, cathepsin C has several structural and functional features that set it apart from other members of the family and enable its selective targeting. It possesses dipeptidyl-peptidase activity (its other common name is dipeptidyl-peptidase I) due to the presence of an additional exclusion domain that also controls its stepwise tetramerization during maturation. In this review article, we summarize the current state of the art regarding the biochemical properties of cathepsin C, its physiological and pathological roles in neutrophils and beyond, and recent advances in the development and evaluation of cathepsin C inhibitors.

Benefit-risk assessment of brensocatib for treatment of non-cystic fibrosis bronchiectasis.

Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile. https://bit.ly/3SbisW3.

Characterization of Eosinophilic Bronchiectasis: A European Multicohort Study.

Rationale: Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described. Objectives: To use multiple datasets available through the European Multicentre Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations. Methods: Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A post hoc analysis of the PROMIS (Inhaled Promixin in the Treatment of Non-Cystic Fibrosis Bronchiectasis) phase 2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with Pseudomonas aeruginosa infection. Measurements and Main Results: A relationship between sputum and blood eosinophil counts was demonstrated in two cohorts. In analysis of 1,007 patients from five countries, 22.6% of patients had blood eosinophil counts of ⩾300 cells/μl. Counts of <100 cells/μl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/μl were associated with both Streptococcus- and Pseudomonas-dominated microbiome profiles. To investigate the relationship of eosinophil counts with exacerbations after controlling for the confounding effects of infection, 144 patients were studied in a clinical trial after treatment with antipseudomonal antibiotics. Compared with patients with blood eosinophil counts of <100 cells/μl (reference), elevated eosinophil counts of 100-299 cells/μl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and ⩾300 cells/μl (hazard ratio, 3.99; 95% confidence interval, 2.20-7.85; P < 0.0001) were associated with shorter time to exacerbation. Conclusions: Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.

Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe.

BackgroundBronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020.MethodsWe retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made.ResultsA total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown “destroyed lobe” (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction.ConclusionsIn spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.

Meta-analysis of efficacy and safety of inhaled ciprofloxacin in non-cystic fibrosis bronchiectasis patients.

No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non-cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial. No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non-cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial. We conducted the present meta-analysis to comprehensively evaluate the feasibility of inhalation of ciprofloxacin in NCFB. Electrical databases Medline and Cochrane library were retrieved from inception through December 2019. Randomised controlled trials (RCT) comparing inhaled ciprofloxacin and placebo were selected. The primary outcomes were time to first exacerbation, frequency of exacerbations and the change in sputum Pseudomonas aeruginosa density. A total of five articles involving six RCT was finally included in the analysis. The time to first exacerbation was significantly prolonged by inhaled ciprofloxacin (hazard ratio: 0.72, 95% confidence interval (CI): 0.63-0.82), with low heterogeneity (I2 = 23%). Inhalation of ciprofloxacin significantly reduced frequency of exacerbations (risk ratio: 0.70, 95% CI: 0.61-0.79) and decreased density of sputum P. aeruginosa (weighted mean difference: -2.11 log10 CFU/g, 95% CI: -2.96 to -1.27 log10 CFU/g) compared with placebo. No significant between-group differences in mortality, adverse events and discontinuation rate were observed. Further indirect treatment comparison showed no differences between the two types of inhaled ciprofloxacin in all outcomes of interest. Ciprofloxacin inhalation treatment significantly prolonged the time to first exacerbation, reduced the frequency of exacerbations and decreased sputum P. aeruginosa density and was well tolerated. Ciprofloxacin inhalation is promising in the treatment of NCFB.

Pulmonary Rehabilitation in Noncystic Fibrosis Bronchiectasis

Background: Current guidelines for the treatment of noncystic fibrosis bronchiectasis (NCFB) recommend pulmonary rehabilitation (PR), but to date, there are few studies that have proven its effectiveness. Objective: The main objective of this study was to examine the effect of PR on pulmonary function tests and exercise capacity. Method: The aim of this study was to systematically review the effects of PR in NCFB on (1) forced expiratory volume in the first second (FEV₁) and (2) exercise capacity evaluated by the 6-min walk test (6MWT) and the incremental shuttle walk test (ISWT). This meta-analysis was undertaken according to PRISMA recommendations. Results: This pair-wise meta-analysis included data obtained from studies that enrolled 529 NCFB patients. The FEV₁ assessment after PR between the active and control group did not show any significant increase (FEV₁ difference 0.084 mL; CI: −0.064, +0.233; p = 0.264), and there was an increasing trend (188 mL; CI: −0 to 0.009, +0.384) at the limits of statistical significance (p = 0.061). Walked distance showed a significant increase in the PR group compared to the control group (ISWT distance difference 070.0 m; CI: 55.2, 84.8; p < 0.001), and this finding was confirmed before and after PR both by the ISWT (68.85 m greater than baseline; CI: 40.52, 97.18; p < 0.001) and by the 6MWT (37.7 m greater than baseline; CI: 20.22, 55.25; p < 0.001). Conclusions: PR improves exercise tolerance in NCFB patients, but it has a modest impact on respiratory function.

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment

PurposeCiprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB).MethodsNLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined.ResultsThe CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9–5.1 μm.ConclusionNovel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.

Bronchiectasis in Turkey: Under the light of national publications

In this review, we aimed to determine the etiopathogenesis, diagnosis and treatment of non-cystic fibrosis bronchiectasis in the light of scientific studies conducted in our country. For this purpose, Pubmed, Web of Science ve Ulakbim TR Dizin were searched and the publications available as of July 2019 were evaluated and the findings of these studies were summarized and presented.

Non-CF bronchiectasis: Orphan disease no longer.

Bronchiectasis is a complex, chronic respiratory condition, characterized by frequent cough and exertional dyspnea due to a range of conditions that include inherited mucociliary defects, inhalational airway injury, immunodeficiency states and prior respiratory infections. For years, bronchiectasis was classified as either being caused by cystic fibrosis or non-cystic fibrosis. Non-cystic fibrosis bronchiectasis, once considered an orphan disease, is more prevalent worldwide in part due to greater availability of chest computed tomographic imaging. Identification of the cause of non-cystic fibrosis bronchiectasis with the use of chest imaging, laboratory testing, and microbiologic assessment of airway secretions can lead to initiation of specific therapies aimed at slowing disease progression. Nonpharmacologic therapies such as airway clearance techniques and pulmonary rehabilitation improve patient symptoms. Inhaled corticosteroids should not be routinely prescribed unless concomitant asthma or COPD is present. Inhaled antibiotics prescribed to individuals with >3 exacerbations per year are well tolerated, reduce airway bacteria load and may reduce the frequency of exacerbations. Likewise, chronic macrolide therapy reduces the frequency of exacerbations. Medical therapies for cystic fibrosis bronchiectasis may not be effective in treatment of non-cystic fibrosis bronchiectasis.

Inhalations of Ultra-low Doses of Melphalan for the Treatment of Non-cystic Fibrosis Bronchiectasis

Inhalations of Ultra-low Doses of Melphalan for the Treatment of Non-cystic Fibrosis Bronchiectasis

Safety and efficacy of the human neutrophil elastase inhibitor BAY 85-8501 for the treatment of non-cystic fibrosis bronchiectasis: A randomized controlled trial

BackgroundThere are only limited treatment options for patients with non-cystic fibrosis bronchiectasis (non-CF BE). Human neutrophil elastase (HNE) is a mediator of tissue destruction in non-CF BE. BAY 85-8501, a selective and reversible HNE inhibitor, could represent a new treatment option for this disease. MethodsThis was a phase 2a, randomized, placebo-controlled, double-blind, parallel-group study. The primary objective was to assess the safety and tolerability of 1 mg BAY 85-8501 once daily (OD) for 28 days compared with placebo in patients with non-CF BE. Secondary objectives were to investigate the effects of 4 weeks of treatment with BAY 85-8501 on health-related quality of life, pulmonary function, and inflammatory and tissue damage biomarkers in sputum, blood and/or urine, and to evaluate the pharmacokinetics of BAY 85-8501. ResultsOverall, 94 patients (mean age, 66 years; 53% male) were randomized (n = 47 per group), and 82 completed the study (BAY 85-8501, n = 37; placebo, n = 45). Treatment-emergent adverse events (TEAEs) occurred in 31 patients (66%) taking BAY 85-8501 and in 36 patients (77%) taking placebo, and were mostly mild or moderate. The serious TEAEs (BAY 85-8501, n = 3; placebo, n = 1) were not considered to be study-drug related.There were no changes in pulmonary function parameters from baseline to end of treatment, and health-related quality of life did not improve in any group. HNE activity in blood after zymosan challenge decreased significantly with BAY 85-8501 treatment (P = 0.0250 versus placebo). There were no significant differences in other biomarkers between treatment groups, with the exception of a small increase in interleukin-8 levels in sputum in the BAY 85-8501 group. Trough plasma concentrations of BAY 85-8501 plateaued after 2 weeks. Conclusions1 mg BAY 85-8501 OD had a favourable safety and tolerability profile when administered for 28 days to patients with non-CF BE. Further studies with a longer treatment duration are needed to evaluate the potential clinical efficacy in this study population.

Brazilian consensus on non-cystic fibrosis bronchiectasis.

ABSTRACTBronchiectasis is a condition that has been increasingly diagnosed by chest HRCT. In the literature, bronchiectasis is divided into bronchiectasis secondary to cystic fibrosis and bronchiectasis not associated with cystic fibrosis, which is termed non-cystic fibrosis bronchiectasis. Many causes can lead to the development of bronchiectasis, and patients usually have chronic airway symptoms, recurrent infections, and CT abnormalities consistent with the condition. The first international guideline on the diagnosis and treatment of non-cystic fibrosis bronchiectasis was published in 2010. In Brazil, this is the first review document aimed at systematizing the knowledge that has been accumulated on the subject to date. Because there is insufficient evidence on which to base recommendations for various treatment topics, here the decision was made to prepare an expert consensus document. The Brazilian Thoracic Association Committee on Respiratory Infections summoned 10 pulmonologists with expertise in bronchiectasis in Brazil to conduct a critical assessment of the available scientific evidence and international guidelines, as well as to identify aspects that are relevant to the understanding of the heterogeneity of bronchiectasis and to its diagnostic and therapeutic management. Five broad topics were established (pathophysiology, diagnosis, monitoring of stable patients, treatment of stable patients, and management of exacerbations). After this subdivision, the topics were distributed among the authors, who conducted a nonsystematic review of the literature, giving priority to major publications in the specific areas, including original articles, review articles, and systematic reviews. The authors reviewed and commented on all topics, producing a single final document that was approved by consensus.

Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

PRS39 - Psychometric Analyses of Pros in Bronchiectasis

To evaluate psychometric properties of the Saint George’s Respiratory Questionnaire Symptoms Domain (SGRQ-SD) and the Quality of Life-Bronchiectasis Respiratory Symptoms Domain (QOL–B-RSD) using data of a phase 3 randomized, placebo-controlled, multicenter study of Ciprofloxacin DPI administered for 28 days on/28 days off or 14 days on/14 days off compared to placebo for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Confirmatory factor analysis (CFA), item response theory (IRT), reliability, criterion validity, construct validity, ability to detect change (responsiveness), and responder definition (RD) thresholds using anchor- and distribution-based methods were assessed for the SGRQ-SD and QOL-B-RSD. CFA and Rasch analysis indicated misfit of the SGRQ-SD and item response categories were poorly distinguished. The Cronbach’s alpha for internal consistency of the SGRQ-SD was moderate (0.646), and convergent validity with dyspnea severity was moderate (0.44). For the QOL-B-RSD, analysis indicated misfit and poorly distinguished response categories for three of nine items. Internal consistency and test-retest reliability of the QOL-B-RSD was good (Cronbach’s alpha=0.81, ICC=0.70), and convergent validity with dyspnea severity was moderate (-0.46). The known-groups validity of the SGRQ-SD and QOL-B-RSD was supported with scores significantly distinguished among the levels of dyspnea severity, and responsiveness of both instruments was supported by the dyspnea criterion measure. RD analyses were limited by the instruments’ relationship with the anchors available in this phase 3 trial. The classic psychometric analyses performed demonstrated good reliability and validity estimates, known groups validity, and responsiveness when dyspnea severity was used as a criterion variable. However, items of the SGRQ-SD demonstrated poorly-ordered responses, or did not distinguish well among respondents per CFA and IRT analyses. Additional qualitative and quantitative research is needed for further development of NCFB patient-reported outcomes.

Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

A Delphi Study of Pharmacotherapy for Noncystic Fibrosis Bronchiectasis

BackgroundPresently, there are no medications approved by regulatory bodies for the treatment of noncystic fibrosis bronchiectasis (NCFB). in addition, most techniques/devices to enhance mucociliary clearance in NCFB have not been rigorously evaluated. Therefore, we performed a Delphi study of clinical experts concerning the treatment of NCFB. MethodsTen individuals with extensive experience with NCFB participated. Questions were posed concerning pharmacotherapy and mucocilary clearance techniques for NCFB. iterative questioning and feedback from previous responses were used with an aim to reach consensus. Consensus was defined as ≥70% agreement of the experts. ResultsThe experts reached consensus concerning several issues including: (1) 10 to 14 days duration of antibiotics for exacerbations of NCFB, (2) Combination antibiotics should not be given for acute exacerbations of NCFB regardless of history of pseudomonas colonization, (3) some type of airway clearance technique should be used for stable NCFB, (4) recommended treatment end points for NCFB include sputum volume, sputum color and exacerbation frequency and (5) recombinant DNA-ase and inhaled corticosteroids should not be routinely used for NCFB. There was some inconsistency in expert responses between the 2 rounds of questions, suggesting that even NCFB experts do not have a completely consistent approach to treatment. ConclusionsNCFB experts reached consensus on several treatment issues. in the absence of rigorous medical evidence, these data supply support for these approaches. several questions posed to the experts did not reach consensus. We would classify these issues as “controversial” and suggest that they are important areas for future research.

Advantages and drawbacks of long-term macrolide use in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis (non-CF) bronchiectasis is a respiratory disease characterized by persistent airway inflammation and dilation of bronchial wall driven by various causes. Patients with bronchiectasis suffer from excessive sputum production, recurrent exacerbations, and progressive airway destruction. Major therapy for bronchiectasis is focused on breaking the "vicious cycle" of mucus stasis, infection, inflammation, and airway destruction. Growing evidences have been shown that macrolides possess immunoregulatory and anti-inflammatory functions beyond their antimicrobial effects. Macrolide antibiotics have been effectively used in the treatment of diffuse panbronchiolitis, CF and bronchiolitis obliterans syndrome. Currently a number of clinical trials were performed to assess macrolide treatment in the management of non-CF bronchiectasis. The purpose of this paper is to review the efficacy and potential risks of these recent studies on the use of macrolides in non-CF bronchiectasis.

Surgical treatment of non-cystic fibrosis bronchiectasis in Brazilian children

To determine the clinical characteristics of patients submitted to surgical treatment for non-cystic fibrosis (CF) bronchiectasis, the indications for surgery, and the results obtained at a referral facility for pediatric thoracic surgery. Between January 1998 and December 2009, we retrospectively reviewed the medical charts of 109 pediatric patients with non-CF bronchiectasis who underwent surgical treatment. These findings were subsequently analyzed by focusing on postoperative complications and long-term results. Of the 109 patients undergoing pulmonary resection, the mean age was 7.6 years (ranging from 1 to 15.5 y-o) with male predominance (59 %). The most common procedure was segmentectomy (43 %) followed by left lower lobectomy (38 %). Minor postoperative complications occurred in 36 % of the patients; the most common was transient atelectasis (26 %), followed by air leak (6 %), and postoperative pain (4 %). There was one death within the 30-day postoperative period, but it was unrelated to the procedure. Eighty-three children were followed after discharge, with a mean follow-up period of 667 days. Sixty-five (76 %) patients showed improvement of clinical symptoms after surgery. Lung resection for the treatment of non-CF bronchiectasis in children is a safe procedure, with no life-treating morbidity and low mortality. This procedure also leads to significant improvements in symptoms and quality of life.

Phase 3 Randomized Study of the Efficacy and Safety of Inhaled Dry Powder Mannitol for the Symptomatic Treatment of Non-Cystic Fibrosis Bronchiectasis

Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis. This study's objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks. Patients with bronchiectasis confirmed by high-resolution CT (HRCT) scan, aged 15 to 80 years, with FEV1≥50% predicted and ≥1 L participated in a randomized, placebo-controlled, double-blind study. Patients with a negative mannitol provocation test were randomized to inhale 320 mg mannitol (n=231) or placebo (n=112) bid for 12 weeks. To further assess safety, the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks. Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George's Respiratory Questionnaire (SGRQ) score. There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks (95% CI, 1.64-7.00; P=.002) between mannitol and placebo; however, this was largely driven by a decrease in sputum weight in the placebo group. This was associated, in turn, with more antibiotic use in the placebo group (50 of 112 [45%]) than in the inhaled mannitol group (85 of 231 [37%]). There was no statistical difference between the groups (P=.304) in total SGRQ score (mannitol, -3.4 points [95% CI, -4.81 to -1.94] vs placebo, -2.1 points [95% CI, -4.12 to -0.09]). In a subgroup study (n=82), patients receiving mannitol showed less small airway mucus plugging on HRCT scan at 12 weeks compared with patients receiving placebo (P=.048). Compliance rates were high, and mannitol was well tolerated with adverse events similar to those of placebo. Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group, a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use. ClinicalTrials.gov; No.: NCT0027753; URL: www.clinicaltrials.gov.

Treatment of Non-Cystic Fibrosis Bronchiectasis

Bronchiectasis is currently growing in importance due to both the increase in the number of diagnoses made as well as the negative impact that its presence has on the baseline disease that generates it. The fundamental aspects in these patients are the colonization and infection of the bronchial mucous by potentially pathogenic microorganisms (PPM), which are the causes in most cases of the start of the chronic inflammatory process resulting in the destruction and dilatation of the bronchial tree that is characteristic in these patients. The treatment of the colonization and chronic bronchial infection in these patients should be based on prolonged antibiotic therapy in its different presentations. Lately, the inhaled form is becoming especially prominent due to its high efficacy and limited production of important adverse effects. However, one must not overlook the fact that the management of patients with bronchiectasis should be multidisciplinary and multidimensional. In addition to antibiotic treatment, the collaboration of different medical and surgical specialties is essential for the management of the exacerbations, nutritional aspects, respiratory physiotherapy, muscle rehabilitation, complications, inflammation and bronchial hyperreactivity and the hypersecretion that characterizes these patients.