Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

In severe, uncontrolled asthma, tezepelumab reduced exacerbations over 1 y regardless of type 2 inflammation level.

SOURCE CITATION: Corren J, Menzies-Gow A, Chupp G, et al. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med. 2023;208:13-24. 37015033.

In COPD with type 2 inflammation despite inhaled triple therapy, dupilumab safely reduced exacerbations.

SOURCE CITATION: Bhatt SP, Rabe KF, Hanania NA, et al; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023;389;205-214.37272521.

Suspected Bronchiectasis and Mortality in Adults With a History of Smoking Who Have Normal and Impaired Lung Function : A Cohort Study.

BACKGROUND: Bronchiectasis in adults with chronic obstructive pulmonary disease (COPD) is associated with greater mortality. However, whether suspected bronchiectasis-defined as incidental bronchiectasis on computed tomography (CT) images plus clinical manifestation-is associated with increased mortality in adults with a history of smoking with normal spirometry and preserved ratio impaired spirometry (PRISm) is unknown. OBJECTIVE: To determine the association between suspected bronchiectasis and mortality in adults with normal spirometry, PRISm, and obstructive spirometry. DESIGN: Prospective, observational cohort. SETTING: The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. PARTICIPANTS: 7662 non-Hispanic Black or White adults, aged 45 to 80 years, with 10 or more pack-years of smoking history. Participants who were former and current smokers were stratified into normal spirometry (n = 3277), PRISm (n = 986), and obstructive spirometry (n = 3399). MEASUREMENTS: Bronchiectasis identified by CT was ascertained using artificial intelligence-based measurements of an airway-to-artery ratio (AAR) greater than 1 (AAR >1), a measure of bronchial dilatation. The primary outcome of "suspected bronchiectasis" was defined as an AAR >1 of greater than 1% plus 2 of the following: cough, phlegm, dyspnea, and history of 2 or more exacerbations. RESULTS: Among the 7662 participants (mean age, 60 years; 52% women), 1352 (17.6%) had suspected bronchiectasis. During a median follow-up of 11 years, 2095 (27.3%) died. Ten-year mortality risk was higher in participants with suspected bronchiectasis, compared with those without suspected bronchiectasis (normal spirometry: difference in mortality probability [Pr], 0.15 [95% CI, 0.09 to 0.21]; PRISm: Pr, 0.07 [CI, -0.003 to 0.15]; obstructive spirometry: Pr, 0.06 [CI, 0.03 to 0.09]). When only CT was used to identify bronchiectasis, the differences were attenuated in the normal spirometry (Pr, 0.04 [CI, -0.001 to 0.08]). LIMITATIONS: Only 2 racial groups were studied. Only 1 measurement was used to define bronchiectasis on CT. Symptoms of suspected bronchiectasis were nonspecific. CONCLUSION: Suspected bronchiectasis was associated with a heightened risk for mortality in adults with normal and obstructive spirometry. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Artificial Intelligence-based CT Assessment of Bronchiectasis: The COPDGene Study.

Background CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans. Purpose To determine the extent of AARs using an artificial intelligence-based chest CT and assess the association of AARs with exacerbations over time. Materials and Methods In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of airway dilatation) in each participant on chest CT scans was determined. Pulmonary exacerbations were prospectively determined through biannual follow-up (from July 2009 to September 2021). Multivariable zero-inflated regression models were used to assess the association between the percentage of airways with AAR greater than 1 and the total number of pulmonary exacerbations over follow-up. Covariates included demographics, lung function, and conventional CT parameters. Results Among 4192 participants (median age, 59 years; IQR, 52-67 years; 1878 men [45%]), 1834 had chronic obstructive pulmonary disease (COPD). During a 10-year follow-up and in adjusted models, the percentage of airways with AARs greater than 1 (quartile 4 vs 1) was associated with a higher total number of exacerbations (risk ratio [RR], 1.08; 95% CI: 1.02, 1.15; P = .01). In participants meeting clinical and imaging criteria of bronchiectasis (ie, clinical manifestations with ≥3% of AARs >1) versus those who did not, the RR was 1.37 (95% CI: 1.31, 1.43; P < .001). Among participants with COPD, the corresponding RRs were 1.10 (95% CI: 1.02, 1.18; P = .02) and 1.32 (95% CI: 1.26, 1.39; P < .001), respectively. Conclusion In ever-smokers with chronic obstructive pulmonary disease, artificial intelligence-based CT measures of bronchiectasis were associated with more exacerbations over time. Clinical trial registration no. NCT00608764 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Schiebler and Seo in this issue.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Host- and Age-Dependent Transcriptional Changes in Mycobacterium tuberculosis Cell Envelope Biosynthesis Genes after Exposure to Human Alveolar Lining Fluid.

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019, and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes into close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic, innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb-host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional, with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay shows that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows a lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status, determined by factors such as age, might play an important role in determining infection outcome.

Healthcare resource utilization, expenditures, and productivity in patients with asthma with and without allergies.

Objective: To compare healthcare resource utilization (HCRU), healthcare expenditures, and work productivity and activity impairment within a general asthma population with persistent asthma and evidence of allergy (PA-EA) and persistent asthma with no evidence of allergy (PA-NEA).Methods: We conducted a retrospective analysis of survey responses and claims from the Observational Study of Asthma Control and Outcomes (OSACO) study. Eligible patients with persistent asthma aged ≥12 years were sent four surveys over 15 months. Regression models were used to assess the association between: (1) PA-EA (defined as a positive response to a survey question about hay fever/seasonal allergies AND ≥1 diagnostic code for atopic conditions) and HCRU and expenditures; and (2) PA-EA and Work Productivity and Activity Impairment (WPAI)-Asthma questionnaire scores (vs. PA-NEA).Results: Adjusted data showed that, vs. PA-NEA (n = 312), patients with PA-EA (n = 971) incurred 1.34-times more all-cause prescriptions (95% confidence interval [CI], 1.20-1.48), $132.79 higher prescription costs (95% CI, $22.03-243.56), and $926.11 higher all-cause total healthcare costs (95% CI, $279.67-1572.54), per 4-month period. Patients with PA-EA were 4.1% less productive while working (95% CI, 3.75-4.48%) and experienced a 6.5% reduction in all activities (95% CI, 6.11-6.88%) vs. those with PA-NEA.Conclusions: Patients with PA-EA had greater HCRU, healthcare expenditures, and lower productivity compared with those patients with PA-NEA. These results highlight the burden of atopy in patients with persistent asthma and underscore the importance of allergic endotype identification for more vigilant disease management.

Impact of allergies on health-related quality of life in patients with asthma.

Objective: To estimate the health-related quality of life (HRQoL) and health utilities among asthma patients with and without comorbid allergies in a managed care population.Methods: This was a retrospective analysis of patient survey responses and pharmacy claims from the Observational Study of Asthma Control and Outcomes (OSACO). Patients ≥12 years-old with persistent asthma received four identical surveys between April-2011 and December-2012. The presence of allergy was identified by a positive response to a survey question about hay fever/seasonal allergies and ≥1 diagnosis-related ICD-9-CM code(s) for allergic conditions. HRQoL instruments included generic utility (EQ-5D-3L [including VAS]), asthma-specific utility (AQL-5D) and asthma-specific health status (Mini Asthma Quality of Life Questionnaire [MiniAQLQ]). Median regression was used for utility scores and Least Squares regression for MiniAQLQ, adjusting for sociodemographic characteristics and smoking.Results: Of the 2681 asthmatics who completed the first survey in the OSACO study, 971 had comorbid allergies. After adjusting for covariates, asthma patients with comorbid allergies had significantly lower MiniAQLQ scores than patients without allergies (-0.489 [95% CI -0.570, -0.409]; p < 0.01), with the greatest decrement/impairment observed for the environmental stimuli domain (-0.729 [95% CI -0.844, -0.613]; p < 0.01). Utility scores were also statistically significantly lower for asthma patients with comorbid allergies compared to those without allergies (EQ-5D, -0.031 [95% CI -0.047, -0.015]; AQL-5D, -0.036 [95% CI -0.042, -0.029]; p < 0.01 each).Conclusions: The presence of allergies with persistent asthma is associated with a significant deleterious impact on several different measures of HRQoL.

Long-term evaluation of response to omalizumab therapy in real life by a novel multimodular approach: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study.

BACKGROUND: The evidence on long-term real-life response measures to omalizumab therapy in moderate to severe asthma is limited. A universal assessment tool is needed to adequately evaluate response to omalizumab in these patients. OBJECTIVE: To design a multimodular response assessment tool and use it to measure and define response to omalizumab therapy in real-world settings. METHODS: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study is a retrospective, long-term, real-life clinical study that evaluates response in individuals with allergic asthma who received omalizumab between 2004 and 2011. The Standardized Measure to Assess Response to Therapy (SMART) tool was designed to define response (1 year before to after treatment) by 3 modules: (1) physician's subjective assessment of asthma symptoms and control; (2) objective assessment of 6 parameters: improvement by 50% or more for asthma exacerbation, steroid bursts, emergency department visits, and hospitalizations; increase in forced expiratory volume in 1 second of 200 mL or greater; and improved Asthma Control Test score of 3 or higher; -and (3) true responders (patient meeting both module 1 and 2 criteria). Response was assessed and compared for 3 modules at desired time points. RESULTS: A total of 198 patients (mean age, 31.7 years [range, 3-77 years]; 98 [49%] female; mean omalizumab therapy duration, 2.49 years [range, 3 months to 8 years]; mean omalizumab dosage, 473 mg every 4 weeks; median baseline IgE level, 433 IU/mL) were included in this analysis. Overall visit adherence was 78%, although the adherence rate decreased annually by 20%. Response rates assessed by SMART modules were 61.3%, 60.8%, and 41.8% at 16 weeks, 84.8%, 72.2%, and 64.6% at 1 year, 82.4%, 71.2%, and 63.2% at 2 years, and 95.1%, 87.8%, and 85.4% at 5 years for modules 1, 2, and 3, respectively. There were no significant adverse reactions. CONCLUSION: The REALITY study has demonstrated long-term effectiveness of omalizumab therapy in individuals with allergic asthma in real-life settings. The SMART tool is promising as a potential standard assessment tool to measure and define response to asthma therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01776177.

Medication use and indicators of poor asthma control in patients with and without allergies.

Background: Approximately two-thirds of people with asthma have some evidence of allergy; their condition differs from nonallergic asthma in terms of predominant symptoms and clinical outcomes. Objective: To compare asthma control and medication use among patients with persistent asthma with evidence of allergy (PA-EA) and patients with persistent asthma with no evidence of allergy (PA-NEA). Methods: A retrospective analysis of survey responses and medication claims data from the Observational Study of Asthma Control and Outcomes study, a prospective survey linked to retrospective claims-based analysis of patients ages ≥ 12 years with persistent asthma in a U.S. health maintenance organization. Evidence of allergy was defined as both a positive response to a survey question about hay fever and/or seasonal allergies and one or more medical diagnostic codes for atopic conditions. Regression models were used to compare asthma control (Asthma Control Questionnaire [ACQ] scores) and asthma medication use between PA-EA and PA-NEA. Results: Adjusted data showed that, versus the patients with PA-NEA (n = 312), patients with PA-EA (n = 971) had higher (worse) 5-item and 6-item ACQ (ACQ-5 and ACQ-6) scores (by 0.34 [95% confidence interval {CI}, 0.24-0.44]; and 0.31 [95% CI, 0.21-0.40], respectively), were more likely to have poorly controlled asthma (ACQ-5 score ≥ 1.5: odds ratio 3.37 [95% CI, 2.07-5.50]; ACQ-6 score ≥ 1.5: odds ratio 3.46 [95% CI, 2.13-5.62]) and less likely to have well-controlled asthma (ACQ-5 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.34]; ACQ-6 score ≤ 0.75: odds ratio 0.21 [95% CI, 0.13-0.35]). Patients with PA-EA also had greater asthma medication use, most notably 2.5 times more prescriptions of high-dose inhaled corticosteroid in a 4-month period (95% CI, 1.21-5.16) and 16.15 times higher odds of chronic oral corticosteroid use (95% CI, 1.50-174.09) versus PA-NEA. Conclusion: The patients with PA-EA versus PA-NEA had worse asthma control and greater medication use. These patients may need more vigilant clinical oversight and treatment management to ensure adequate asthma control.

The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model.

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition.

BACKGROUND AND OBJECTIVE: Bronchiectasis manifests as recurrent respiratory infections and reduced lung function. Airway dilation, which is measured as the ratio of the diameters of the bronchial lumen (B) and adjacent pulmonary artery (A), is a defining radiological feature of bronchiectasis. A challenge to equating the bronchoarterial (BA) ratio to disease severity is that the diameters of airway and vessel in health are not established. We sought to explore the variability of BA ratio in never-smokers without pulmonary disease and its associations with lung function. METHODS: Objective measurements of the BA ratio on volumetric computed tomography (CT) scans and pulmonary function data were collected in 106 never-smokers. The BA ratio was measured in the right upper lobe apical bronchus (RB1) and the right lower lobe basal posterior bronchus. The association between the BA ratio and forced expiratory volume in 1 s (FEV1 ) was assessed using regression analysis. RESULTS: The BA ratio was 0.79 ± 0.16 and was smaller in more peripheral RB1 bronchi (P < 0.0001). The BA ratio was >1, a typical threshold for bronchiectasis, in 10 (8.5%) subjects. Subjects with a BA ratio >1 versus ≤1 had smaller artery diameters (P < 0.0001) but not significantly larger bronchial lumens. After adjusting for age, gender, race and height, the BA ratio was directly related to FEV1 (P = 0.0007). CONCLUSION: In never-smokers, the BA ratio varies by airway generation and is associated with lung function. A BA ratio >1 is driven by small arteries. Using artery diameter as reference to define bronchial dilation seems inappropriate.

Suspecting non-cystic fibrosis bronchiectasis: What the busy primary care clinician needs to know.

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterised by irreversibly and abnormally dilated airways, persistent cough, excessive sputum production and recurrent pulmonary infections. In the last several decades, its prevalence has increased, making it likely to be encountered in the primary care setting. The aim was to review the clinical presentation and diagnosis of NCFB, with an emphasis on the role of computed tomography (CT). METHODS: For this review, trials and reports were identified from PubMed/Medline and ClinicalTrials.gov from the US NIH and the Cochrane Register of Controlled Trials. The search used keywords: bronchiectasis, non-cystic fibrosis bronchiectasis, chronic pulmonary infection and computed tomography. No date/language restrictions were used. RESULTS: Non-cystic fibrosis bronchiectasis often coexists with other respiratory conditions, such as chronic obstructive pulmonary disease. The prevalence of NCFB is increasing, particularly in women and older individuals, possibly as a result of increased physician awareness and widespread use of CT, which is the gold standard for the diagnosis of NCFB. CT can assist in identifying an underlying cause of NCFB and determining the extent and severity of the disease. DISCUSSION: Non-cystic fibrosis bronchiectasis should be suspected in the primary care setting in patients with chronic cough, purulent sputum and frequent respiratory infections that tend to resolve slowly or partially. Early diagnosis and determination of the extent and severity of the disease by CT and other tests are critical to establish therapy to improve quality of life and potentially slow progressive decline of lung function in patients with NCFB.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.