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1.
Respir Med ; 227: 107661, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729529

ABSTRACT

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.


Subject(s)
Anti-Bacterial Agents , Biofilms , Drug Delivery Systems , Respiratory Tract Infections , Humans , Biofilms/drug effects , Administration, Inhalation , Anti-Bacterial Agents/administration & dosage , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Drug Resistance, Bacterial , Streptococcus pneumoniae/drug effects , Liposomes , Bronchiectasis/drug therapy , Bronchiectasis/microbiology , Haemophilus influenzae/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Cystic Fibrosis/microbiology , Cystic Fibrosis/drug therapy , Cystic Fibrosis/complications
2.
BMJ Open Respir Res ; 11(1)2024 May 07.
Article in English | MEDLINE | ID: mdl-38719503

ABSTRACT

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.


Subject(s)
Bronchiectasis , Expectorants , Multicenter Studies as Topic , Quality of Life , Thioglycolates , Thiophenes , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Bronchiectasis/drug therapy , Disease Progression , Double-Blind Method , Expectorants/therapeutic use , Randomized Controlled Trials as Topic , Thioglycolates/therapeutic use , Thiophenes/therapeutic use , Treatment Outcome
3.
Respir Res ; 25(1): 211, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762736

ABSTRACT

BACKGROUND: Bronchiectasis is a condition characterized by abnormal and irreversible bronchial dilation resulting from lung tissue damage and can be categorized into two main groups: cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Both diseases are marked by recurrent infections, inflammatory exacerbations, and lung damage. Given that infections are the primary drivers of disease progression, characterization of the respiratory microbiome can shed light on compositional alterations and susceptibility to antimicrobial drugs in these cases compared to healthy individuals. METHODS: To assess the microbiota in the two studied diseases, 35 subjects were recruited, comprising 10 NCFB and 13 CF patients and 12 healthy individuals. Nasopharyngeal swabs and induced sputum were collected, and total DNA was extracted. The DNA was then sequenced by the shotgun method and evaluated using the SqueezeMeta pipeline and R. RESULTS: We observed reduced species diversity in both disease cohorts, along with distinct microbial compositions and profiles of antimicrobial resistance genes, compared to healthy individuals. The nasopharynx exhibited a consistent microbiota composition across all cohorts. Enrichment of members of the Burkholderiaceae family and an increased Firmicutes/Bacteroidetes ratio in the CF cohort emerged as key distinguishing factors compared to NCFB group. Staphylococcus aureus and Prevotella shahii also presented differential abundance in the CF and NCFB cohorts, respectively, in the lower respiratory tract. Considering antimicrobial resistance, a high number of genes related to antibiotic efflux were detected in both disease groups, which correlated with the patient's clinical data. CONCLUSIONS: Bronchiectasis is associated with reduced microbial diversity and a shift in microbial and resistome composition compared to healthy subjects. Despite some similarities, CF and NCFB present significant differences in microbiome composition and antimicrobial resistance profiles, suggesting the need for customized management strategies for each disease.


Subject(s)
Bronchiectasis , Cystic Fibrosis , Microbiota , Humans , Bronchiectasis/microbiology , Bronchiectasis/drug therapy , Bronchiectasis/diagnosis , Cystic Fibrosis/microbiology , Cystic Fibrosis/drug therapy , Cystic Fibrosis/diagnosis , Male , Female , Microbiota/physiology , Microbiota/drug effects , Adult , Middle Aged , Sputum/microbiology , Young Adult , Cohort Studies , Aged
4.
J Med Econ ; 27(1): 671-677, 2024.
Article in English | MEDLINE | ID: mdl-38646702

ABSTRACT

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic progressive respiratory disorder occurring at a rate ranging from 4.2 to 278.1 cases per 100,000 persons, depending on age, in the United States. For many patients with NCFB, the presence of Pseudomonas aeruginosa (PA) makes treatment more complicated and typically has worse outcomes. Management of NCFB can be challenging, warranting a better understanding of the burden of illness for NCFB, treatments applied, healthcare resources used, and subsequent treatment costs. Comparing patients diagnosed with exacerbated NCFB, with or without PA on antibiotic utilization, treatments, and healthcare resources utilization and costs was the purpose of this study. MATERIALS AND METHODS: This was a retrospective cohort study of commercial claims from IQVIA's PharMetrics Plus database (January 1,2006-December 31, 2020). Study patients with a diagnosis of NCFB were stratified into two groups based on the presence or absence of PA, then followed to identify demographic characteristics, comorbid conditions, antibiotic treatment regimen prescribed, healthcare resources utilized, and costs of care. RESULTS: The results showed that patients with exacerbated NCFB who were PA+ had significantly more oral antibiotic fills per patient per year, more inpatient admissions with a longer length of stay, and more outpatient encounters than those who were PA-. For costs, PA+ patients also had significantly greater total healthcare costs per patient when compared to those who were PA-. CONCLUSION: Exacerbated NCFB with PA+ was associated with increased antibiotic usage, greater resource utilization, and increased costs. The major contributor to the cost differences was the use of inpatient services. Treatment strategies aimed at reducing the need for inpatient treatment could lessen the disparities observed in patients with NCFB.


Subject(s)
Anti-Bacterial Agents , Bronchiectasis , Health Resources , Pseudomonas Infections , Pseudomonas aeruginosa , Humans , Bronchiectasis/economics , Bronchiectasis/drug therapy , Female , Retrospective Studies , Male , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/economics , Pseudomonas Infections/drug therapy , Pseudomonas Infections/economics , Adult , United States , Health Resources/statistics & numerical data , Health Resources/economics , Aged , Insurance Claim Review , Comorbidity , Length of Stay/economics , Health Expenditures/statistics & numerical data
6.
Ann Clin Microbiol Antimicrob ; 23(1): 23, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38449006

ABSTRACT

BACKGROUND: The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. METHODS: Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. RESULTS: Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P < 0.05). CONCLUSIONS: Our study contributes to the understanding of the species diversity of Nocardia isolates in Henan, China, and the clinical characteristics of patients with pulmonary nocardiosis infections. Clinical and microbiologic differences between patients with and without bronchiectasis. These findings will contribute to the early diagnosis and treatment of patients.


Subject(s)
Bronchiectasis , Diabetes Mellitus , Nocardia Infections , Nocardia , Pulmonary Disease, Chronic Obstructive , Humans , Nocardia/genetics , RNA, Ribosomal, 16S/genetics , Trimethoprim, Sulfamethoxazole Drug Combination , Nocardia Infections/drug therapy , China , Bronchiectasis/drug therapy , Drug Resistance
8.
Ann Clin Microbiol Antimicrob ; 23(1): 15, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38350983

ABSTRACT

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.


Subject(s)
Bacterial Infections , Bronchiectasis , Methicillin-Resistant Staphylococcus aureus , Respiratory Insufficiency , Adult , Humans , Escherichia coli , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bronchiectasis/drug therapy , Bronchiectasis/epidemiology , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Fibrosis , Respiratory Insufficiency/drug therapy , Drug Resistance, Multiple, Bacterial
9.
BMJ Open Respir Res ; 11(1)2024 02 22.
Article in English | MEDLINE | ID: mdl-38387995

ABSTRACT

BACKGROUND: Chronic airway diseases have been associated with an increased risk of tuberculosis (TB); however, data in patients with bronchiectasis is limited. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. This study investigated whether statin treatment could reduce the risk of TB in patients with bronchiectasis. METHODS: We conducted a retrospective cohort study using a nationwide population database of patients with bronchiectasis who did or did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time were measured for the impact of statin use. The primary outcome was the incidence of new-onset TB. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to estimate HRs with 95% CIs for TB incidence among patients with bronchiectasis. RESULTS: Patients with bronchiectasis receiving statin treatment had a decreased risk of TB. After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users (95% CI 0.40 to 0.88; p=0.0087). Additionally, compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32 (95% CI 0.12 to 0.87; p=0.0255). CONCLUSIONS: Statin treatment demonstrated a dose-dependent protective effect and was associated with a reduced risk of TB in patients with bronchiectasis. These findings suggest that statins may play a role in lowering TB risk by modulating airway inflammation in this patient population.


Subject(s)
Bronchiectasis , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Tuberculosis , Humans , Retrospective Studies , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cohort Studies , Taiwan/epidemiology , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Tuberculosis/drug therapy , Bronchiectasis/drug therapy , Bronchiectasis/epidemiology
10.
Curr Opin Pulm Med ; 30(3): 235-242, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38345396

ABSTRACT

PURPOSE OF REVIEW: Bronchiectasis is a chronic respiratory disease characterized by dilated airways, persistent sputum production and recurrent infective exacerbations. The microbiology of bronchiectasis includes various potentially pathogenic microorganisms including Pseudomonas aeruginosa which is commonly cultured from patients' sputum. P. aeruginosa is difficult to eradicate and frequently exhibits antimicrobial resistance. Bacteriophage therapy offers a novel and alternative method to treating bronchiectasis and can be used in conjunction with antibiotics to improve patient outcome. RECENT FINDINGS: Thirteen case reports/series to date have successfully used phages to treat infections in bronchiectasis patients, however these studies were constrained to few patients ( n  = 32) and utilized personalized phage preparations and adjunct antibiotics. In these studies, phage therapy was delivered by inhalation, intravenously or orally and was well tolerated in most patients without any unfavourable effects. Favourable clinical or microbiological outcomes were seen following phage therapy in many patients. Longitudinal patient follow-up reported regrowth of bacteria and phage neutralization in some studies. There are five randomized clinical controlled trials ongoing aiming to use phage therapy to treat P. aeruginosa associated respiratory conditions, with limited results available to date. SUMMARY: More research, particularly robust clinical trials, into how phages can clear respiratory infections, interact with resident microbiota, and how bacteria might develop resistance will be important to establish to ensure the success of this promising therapeutic alternative.


Subject(s)
Bacteriophages , Bronchiectasis , Pseudomonas Infections , Humans , Anti-Bacterial Agents/therapeutic use , Bronchiectasis/drug therapy , Pseudomonas Infections/therapy , Respiratory System , Pseudomonas aeruginosa
11.
Eur Respir Rev ; 33(171)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38296344

ABSTRACT

INTRODUCTION: Pseudomonas aeruginosa is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected success rate of eradication in clinical practice is not known. METHODS: We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating P. aeruginosa eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for P. aeruginosa at 12 months after eradication treatment. Cystic fibrosis was excluded. RESULTS: Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month P. aeruginosa eradication rate of 40% (95% CI 34-45%; p<0.00001), with no significant heterogeneity (I2=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%). CONCLUSION: Eradication treatment in bronchiectasis results in eradication of P. aeruginosa from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.


Subject(s)
Bronchiectasis , Cystic Fibrosis , Pseudomonas Infections , Adult , Humans , Pseudomonas Infections/diagnosis , Pseudomonas Infections/drug therapy , Pseudomonas Infections/chemically induced , Administration, Inhalation , Anti-Bacterial Agents/adverse effects , Bronchiectasis/diagnosis , Bronchiectasis/drug therapy , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/drug therapy , Pseudomonas aeruginosa
12.
Expert Rev Clin Pharmacol ; 17(2): 157-164, 2024.
Article in English | MEDLINE | ID: mdl-38224017

ABSTRACT

BACKGROUND: This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in bronchiectasis. RESEARCH DESIGN AND METHODS: A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. RESULTS: Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81-1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84-1.33) for acute exacerbation, and 1.06 (95% CI 0.66-1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43-0.81; BUD/FOR HR 0.68, 95% CI 0.50-0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26-0.86) and all-cause hospitalization (HR 0.55, 95% 0.37-0.80) compared to FLU/SAL. CONCLUSION: Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.


Subject(s)
Bronchiectasis , Pulmonary Disease, Chronic Obstructive , Humans , Muscarinic Antagonists/adverse effects , Retrospective Studies , Adrenergic beta-2 Receptor Agonists/adverse effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Formoterol Fumarate , Adrenal Cortex Hormones , Fluticasone-Salmeterol Drug Combination/therapeutic use , Bronchiectasis/drug therapy , Administration, Inhalation , Bronchodilator Agents , Drug Therapy, Combination
14.
Semin Respir Crit Care Med ; 45(1): 114-127, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38154470

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by Aspergillus fumigatus in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay between the fungus and the host immune response, which causes persistent inflammation and tissue damage. Patients present with chronic cough, wheezing, and dyspnea due to uncontrolled asthma. Characteristic symptoms include the expectoration of brownish mucus plugs. Radiographic findings often reveal fleeting pulmonary infiltrates, bronchiectasis, and mucus impaction. However, the definitive diagnosis of ABPA requires a combination of clinical, radiological, and immunological findings. The management of ABPA aims to reduce symptoms, prevent disease progression, and minimize the future risk of exacerbations. The treatment approach involves systemic glucocorticoids or antifungal agents to suppress the inflammatory response or fungal growth and prevent exacerbations. Biological agents may be used in patients with severe disease or glucocorticoid dependence. This review provides an overview of the clinical manifestations and current treatment options for ABPA.


Subject(s)
Aspergillosis, Allergic Bronchopulmonary , Asthma , Bronchiectasis , Cystic Fibrosis , Humans , Aspergillosis, Allergic Bronchopulmonary/diagnosis , Aspergillosis, Allergic Bronchopulmonary/drug therapy , Asthma/drug therapy , Aspergillus fumigatus , Cystic Fibrosis/complications , Bronchiectasis/drug therapy , Glucocorticoids/therapeutic use
15.
Pulm Pharmacol Ther ; 84: 102283, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38141851

ABSTRACT

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.


Subject(s)
Acetylcysteine , Bronchiectasis , Adult , Humans , Male , Aged , Acetylcysteine/adverse effects , Quality of Life , Pilot Projects , Bronchiectasis/drug therapy , Inflammation/drug therapy , Anti-Inflammatory Agents/adverse effects , Double-Blind Method
17.
BMJ Case Rep ; 16(11)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37973540

ABSTRACT

A woman in her 70s with a history of nodular bronchiectatic Mycobacterium avium complex pulmonary disease (MAC-PD) presented with an exacerbated productive cough and worsening findings on chest imaging. Although repeated sputum culture tests were negative for acid-fast bacilli and only revealed normal respiratory flora, a bronchoscopy identified Nocardia sp. Consequently, she was diagnosed with pulmonary nocardiosis and was successfully treated with levofloxacin. It is known that pulmonary nocardiosis can manifest in immunocompetent individuals with bronchiectasis. For cases of refractory nodular bronchiectatic MAC-PD, it is vital to consider bronchoscopy to identify potential co-infections, such as Nocardia.


Subject(s)
Bronchiectasis , Lung Diseases , Mycobacterium avium-intracellulare Infection , Nocardia Infections , Nocardia , Female , Humans , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/complications , Mycobacterium avium-intracellulare Infection/diagnosis , Mycobacterium avium-intracellulare Infection/drug therapy , Bronchiectasis/complications , Bronchiectasis/diagnostic imaging , Bronchiectasis/drug therapy , Lung Diseases/diagnostic imaging , Lung Diseases/drug therapy , Nocardia Infections/diagnosis , Nocardia Infections/diagnostic imaging
18.
BMC Infect Dis ; 23(1): 700, 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37858082

ABSTRACT

BACKGROUND: In Thailand, the incidence of community-acquired pseudomonal pneumonia among 60- to 65-year-olds ranges from 10.90% to 15.51%, with a mortality rate of up to 19.00%. Antipseudomonal agents should be selected as an empirical treatment for elderly patients at high risk for developing this infection. The purpose of this study was to identify risk factors and develop a risk predictor for Pseudomonas aeruginosa infection in older adults with community-acquired pneumonia (CAP). METHODS: A retrospective data collection from an electronic database involved the elderly hospitalized patients with P. aeruginosa- and non-P. aeruginosa-causing CAP, admitted between January 1, 2016, and June 30, 2021. Risk factors for P. aeruginosa infection were analysed using logistic regression, and the instrument was developed by scoring each risk factor based on the beta coefficient and evaluating discrimination and calibration using the area under the receiver operating characteristic curve (AuROC) and observed versus predicted probability (E/O) ratio. RESULTS: The inclusion criteria were met by 81 and 104 elderly patients diagnosed with CAP caused by P. aeruginosa and non-P. aeruginosa, respectively. Nasogastric (NG) tube feeding (odd ratios; OR = 40.68), bronchiectasis (B) (OR = 4.13), immunocompromised condition (I) (OR = 3.76), and other chronic respiratory illnesses (r) such as atelectasis, pulmonary fibrosis, and lung bleb (OR = 2.61) were the specific risk factors for infection with P. aeruginosa. The "60-B-r-I-NG" risk score was named after the 4 abbreviated risk variables and found to have good predicative capability (AuROC = 0.77) and accuracy comparable to or near true P. aeruginosa infection (E/O = 1). People who scored at least two should receive empirically antipseudomonal medication. CONCLUSIONS: NG tube feeding before admission, bronchiectasis, immunocompromisation, atelectasis, pulmonary fibrosis and lung bleb were risk factors for pseudomonal CAP in the elderly. The 60-B-r-I-NG was developed for predicting P. aeruginosa infection with a high degree of accuracy, equal to or comparable to the existing P. aeruginosa infection. Antipseudomonal agents may be started in patients who are at least 60 years old and have a score of at least 2 in order to lower mortality and promote the appropriate use of these medications.


Subject(s)
Bronchiectasis , Community-Acquired Infections , Pneumonia , Pseudomonas Infections , Pulmonary Atelectasis , Humans , Aged , Middle Aged , Pseudomonas Infections/drug therapy , Retrospective Studies , Pneumonia/epidemiology , Pneumonia/drug therapy , Community-Acquired Infections/drug therapy , Bronchiectasis/drug therapy , Chronic Disease , Pseudomonas aeruginosa , Pulmonary Atelectasis/drug therapy , Fibrosis , Anti-Bacterial Agents/therapeutic use
19.
Clin Chest Med ; 44(4): 731-742, 2023 12.
Article in English | MEDLINE | ID: mdl-37890912

ABSTRACT

Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured. The identification of the cause of bronchiectasis and/or coexisting diseases is important because it may affect therapeutic strategies. Airway clearance is the mainstay of bronchiectasis management. It can include multiple breathing techniques, devices, and mucoactive agents. The exact airway clearance regimen should be customized to each individual patient. Chronic pathogenic airway bacteria, such as Pseudomonas aeruginosa, may warrant consideration of eradication therapy and/or chronic use of maintenance inhaled antibiotics.


Subject(s)
Bronchiectasis , Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Bronchiectasis/therapy , Bronchiectasis/drug therapy , Lung , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Lung Diseases/complications , Nontuberculous Mycobacteria , Anti-Bacterial Agents/therapeutic use
20.
Antimicrob Agents Chemother ; 67(11): e0100323, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37843254

ABSTRACT

This study retrospectively analyzed the treatment outcomes of 110 patients with non-cavitary nodular bronchiectatic-type Mycobacterium avium complex pulmonary disease who received intermittent or daily treatment with a three-drug oral antibiotic regimen (i.e., a macrolide, ethambutol, and rifampin) at a tertiary referral center in South Korea. Among these patients, 36 had sputum smear positivity. Of these 36 patients, intermittent treatment led to a lower culture conversion rate than daily treatment [50.0% (8/16) vs 85.0% (17/20), P = 0.034].


Subject(s)
Bronchiectasis , Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Mycobacterium avium Complex , Retrospective Studies , Sputum/microbiology , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/microbiology , Bronchiectasis/drug therapy , Bronchiectasis/microbiology , Anti-Bacterial Agents/therapeutic use , Lung Diseases/drug therapy , Lung Diseases/microbiology , Treatment Outcome
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