Chronic Bronchial Infection Research Articles

Bronchiectasis-COPD Overlap Syndrome: Role of Peripheral Eosinophil Count and Inhaled Corticosteroid Treatment.

Both chronic obstructive pulmonary disease and bronchiectasis are highly prevalent diseases. In both cases, inhaled corticosteroids (ICs) are associated with a decrease in exacerbations in patients with a high peripheral blood eosinophil count (BEC), but it is still not known what occurs in bronchiectasis-COPD overlap syndrome (BCOS). The present study aimed to assess the effect of ICs on various outcomes in patients with BCOS, according to BEC values. We undertook a post-hoc analysis of a cohort of 201 GOLD II-IV COPD patients with a long-term follow-up (median 74 [IQR: 40-106] months). All participants underwent computerized tomography and 115 (57.2%) had confirmed BCOS. A standardized clinical protocol was followed and two sputum samples were collected at each medical visit (every 3-6 months), whenever possible. During follow-up, there were 68 deaths (59.1%), and the mean rate of exacerbations and hospitalizations per year was 1.42 (1.2) and 0.57 (0.83), respectively. A total of 44.3% of the patients presented at least one pneumonic episode per year. The mean value of eosinophils was 402 (112) eosinophils/µL, with 27 (23.5%), 63 (54.8%), and 25 patients (21.7%) presenting, respectively, less than 100, 101-300, and more than 300 eosinophils/µL. A total of 84 patients (73.1%) took ICs. The higher the BEC, the higher the annual rate of exacerbations and hospitalizations. Patients with less than 100 eosinophils/µL presented more infectious events (incident exacerbations, pneumonic episodes, and chronic bronchial infection via pathogenic bacteria). Only those patients with eosinophilia (>300 eosinophils/µL) treated with ICs decreased the number (1.77 (1.2) vs. 1.08 (0.6), p < 0.001) and the severity (0.67 (0.8) vs. 0.35 (0.5), p = 0.011) of exacerbations, without any changes in the other infectious outcomes or mortality. In conclusion, ICs treatment in patients with BCOS with increased BEC decreased the number and severity of incident exacerbations without any negative influence on other infectious outcomes (incidence of pneumonia or chronic bronchial infection).

Efficacy and Safety of Dry Powder Antibiotics: A Narrative Review.

The use of inhaled antibiotics was initially almost exclusively confined to patients with cystic fibrosis (CF). However, it has been extended in recent decades to patients with non-CF bronchiectasis or chronic obstructive pulmonary disease who present with chronic bronchial infection by potentially pathogenic microorganisms. Inhaled antibiotics reach high concentrations in the area of infection, which enhances their effect and enables their long-term administration to defeat the most resistant infections, while minimizing possible adverse effects. New formulations of inhaled dry powder antibiotics have been developed, providing, among other advantages, faster preparation and administration of the drug, as well as avoiding the requirement to clean nebulization equipment. In this review, we analyze the advantages and disadvantages of the different types of devices that allow the inhalation of antibiotics, especially dry powder inhalers. We describe their general characteristics, the different inhalers on the market and the proper way to use them. We analyze the factors that influence the way in which the dry powder drug reaches the lower airways, as well as aspects of microbiological effectiveness and risks of resistance development. We review the scientific evidence on the use of colistin and tobramycin with this type of device, both in patients with CF and with non-CF bronchiectasis. Finally, we discuss the literature on the development of new dry powder antibiotics.

Advances in inhaled antibiotics for management of respiratory tract infections.

The incidence of bacterial respiratory tract infections is growing. In a context of increasing antibiotic resistance and lack of new classes of antibiotics, inhaled antibiotics emerge as a promising therapeutic strategy. Although they are generally used for cystic fibrosis, their use in other conditions is becoming more frequent, including no-cystic fibrosis bronchiectasis, pneumonia and mycobacterial infections. Inhaled antibiotics exert beneficial microbiological effects in bronchiectasis and chronic bronchial infection. In nosocomial and ventilator-associated pneumonia, aerosolized antibiotics improve cure rates and bacterial eradication. In refractory Mycobacterium avium complex infections, amikacin liposome inhalation suspension is more effective in achieving long-lasting sputum conversion. In relation to biological inhaled antibiotics (antimicrobial peptides, interfering RNA and bacteriophages), currently in development, there is no still enough evidence that support their use in clinical practice. The effective antimicrobiological activity of inhaled antibiotics, added to their potential to overcoming resistances to systemic antibiotics, make inhaled antibiotics a plausible alternative.

Inhaled Colistimethate Sodium in the Management of Patients with Bronchiectasis Infected by Pseudomonas aeruginosa: A Narrative Review of Current Evidence.

International guidelines on the treatment of bronchiectasis indicate that the use of inhaled antibiotics is effective, especially in symptomatic chronic bronchial infection (CBI) due to Pseudomonas aeruginosa (PA). To date, however, no such treatment has been approved by regulatory agencies. Of the inhaled antibiotics on the market, colistimethate sodium (colistin) is one of the most used in many countries, either in its nebulized presentation or as dry powder. Among the characteristics of this antibiotic, it is worth noting that its main target is the lipopolysaccharide in the outer membrane of the cell wall of gram-negative bacteria and that it has a low rate of resistance to PA (<1%). Most observational studies have shown that the use of colistin in patients with bronchiectasis and CBI due to PA results in a decrease in both the number and severity of exacerbations, an improvement in quality of life, a decrease in sputum volume and purulence, and a high rate of PA eradication, although there are no clear differences with respect to other inhaled antibiotics. However, the lack of randomized clinical trials (RCT) with positive results for its main variable (exacerbations) in an intention-to-treat analysis has prevented its approval by regulatory agencies as a formal indication for use in bronchiectasis. The PROMIS program, made up of two RCT with identical methodology, is currently underway. The first of these RCT (already concluded) has demonstrated a clearly positive effect on the group randomized to colistin in its main variable (number of annual exacerbations), while the results of the second are still pending. This review presents exhaustive information on the pharmacological and microbiological characteristics of colistin, the results of the studies carried out to date, and the future challenges associated with this treatment.

The BATTLE study: Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis. Study protocol of a double blind, randomized, placebo-controlled trial: study protocol

BackgroundPatients with bronchiectasis typically suffer from chronic symptoms such as a productive cough with or without exacerbations leading to hospitalization, causing reduced quality of life (QoL) and mortality. Long-term inhaled antibiotics to treat chronic bronchial infection is registered for use in cystic fibrosis (CF) bronchiectasis. However, in patients with non-CF bronchiectasis data on long-term antibiotics are limited. ObjectiveTo investigate the effectiveness of maintenance tobramycin inhalation solution (TIS) in bronchiectasis patients without cystic fibrosis. Study designThe BATTLE study is a randomized, double blind placebo controlled, multicenter study in the Netherlands performed in patients aged ≥18-year-old with confirmed bronchiectasis, at least two exacerbations in the preceding year, and minimal one positive sputum culture with gram negative pathogens or Staphylococcus aureus, sensitive to tobramycin in the preceding year and at baseline. Patients will be treated with TIS once daily (OD) or placebo (saline 0.9%) OD for 52 weeks followed by a run-out period of 4 weeks after the last dose. The primary outcome is the yearly rate of pulmonary exacerbations. Among secondary outcome parameters are time to exacerbation, lung function, QoL, microbiological evaluation and safety. DiscussionThe BATTLE study is designed to determine the efficacy and safety of maintenance TIS OD in bronchiectasis patients colonized by different pathogens and could lead to important new evidence for TIS therapy in this population.The BATTLE study is registered in Clinical trials.gov with registration number: NCT02657473.

Profile of patients with post-tuberculosis bronchiectasis in a tertiary care hospital in Brazil

Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.

Pathophysiology of Chronic Bronchial Infection in Bronchiectasis

Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus are the most common bacteria related to chronic bronchial infection. Non-tuberculous mycobacteria, fungi and respiratory viruses are also present during clinical stability, and may increase the risk of acute exacerbation. Chronic inflammation is present in bronchiectasis, especially neutrophilic inflammation. However, macrophages and eosinophils also play a key role in the disease. Finally, airway epithelium has innate mechanisms such as mucociliary clearance and antibacterial molecules like mucins and antimicrobial peptides that protect the airways from pathogens. This review addresses how the persistence of microorganisms in the airways and the imbalance of the immune system contribute to the development of chronic bronchial infection in bronchiectasis.

Bronchiectasis: A pulmonary disease with systemic consequences.

Bronchiectasis: A pulmonary disease with systemic consequences.

Inhaled Corticosteroids in Adults with Non-cystic Fibrosis Bronchiectasis: From Bench to Bedside. A Narrative Review.

Due to their potent anti-inflammatory capacity (particularly in predominantly eosinophilic inflammation) and immunosuppressive properties, inhaled corticosteroids (ICSs) are widely used in asthmatic patients and also in individuals with chronic obstructive pulmonary disease (COPD) who suffer multiple exacerbations or have peripheral eosinophilia. However, there is little evidence for their use in non-cystic fibrosis bronchiectasis (hereafter, bronchiectasis). According to data extracted from large databases of bronchiectasis in adults, ICSs are used in more than 50% of patients without any scientific evidence to justify their efficacy and contrary to the recommendations of international guidelines on bronchiectasis that generally advise against their use. Indeed, bronchiectasis is a disease with predominantly neutrophilic inflammation and a high likelihood of chronic bacterial bronchial infection. Furthermore, it is known that due to their immunosuppressive properties, ICSs can induce an increase in bacterial infections. This manuscript aims to review the basic properties of ICSs, how they impact bronchiectasis in adults, the current position of international guidelines on this treatment, and the current indications and future challenges related to ICS use in bronchiectasis.

Response to inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis and chronic bronchial infection unrelated to Pseudomonas aeruginosa.

Inhaled antibiotics reduce the frequency of exacerbations. The objective was to assess the efficacy of inhaled ceftazidime in patients with non-cystic fibrosis bronchiectasis (NCFB) and concomitant chronic bronchial infection (CBI) caused by potentially pathogenic microorganisms (PPM) other than Pseudomonas aeruginosa (PA). Quasi-experimental study in 21 patients with exacerbations who developed CBI by a PPM other than PA. Bacterial infection was resolved in 85.7% patients. Rehospitalizations, length of hospital stay, moderate exacerbations and blood levels of CRP decreased significantly. In addition, SGRQ questionnaire also decreased more than 4 points in 57.1% of the patients. The results suggest that inhaled ceftazidime in NCFB unrelated to PA is a plausible alternative to the standard therapies used in clinical practice.

Inhalation of antibiotics in the treatment of bronchopulmonal infection

An analysis of the current treatment protocol for lower respiratory tract infection using inhaled antibiotics is presented. Information about the pathophysiology and features of pathogens of bronchopulmonary infection in patients suffering from cystic fibrosis, nosocomial pneumonia, chronic obstructive pulmonary disease, and bronchiectasis of various etiologies is considered. The advantages and applications of inhaled antibiotics in the treatment of this category of patients are discussed. It has been established that acute and chronic infectious diseases of the lower respiratory tract are often the cause of severe human diseases and one of the leading causes of infectious mortality worldwide. Early initiation of adequate antibiotic therapy, especially in patients with a tendency to develop chronic inflammation, improves disease prognosis. However, mortality and the resistance of pathogens in this category of patients remain high. Traditional oral or parenteral antibiotic therapy does not achieve bactericidal concentrations in the lungs. Increasing dosages and combining antibiotics increases the likelihood of toxicity, superinfection, and resistance and causes undesirable side effects. Inhalation of antibiotics allows the delivery of higher concentrations directly to the lesion, thereby affecting the causative agents of the infectious process effectively while minimizing potential systemic toxicity. The large surface area of the alveoli and the thin epithelial layer provide a favorable environment for the deposition of inhaled drugs. Acute and chronic gram-negative bronchial infection caused by certain types of opportunistic microorganisms causes chronic inflammation, which leads to airway remodeling, damage to local defense mechanisms, further persistence of respiratory pathogens, and the formation of antibiotic resistance. In these cases, the use of inhaled forms of antibiotics has significant advantages in terms of effectiveness, stabilizing lung function and reducing the frequency of hospitalization, which improves quality of life and the need for systemic antibiotic therapy, reduces the risk of side effects, and reduces the cost of treatment. The results of the work can be useful for both therapists and pulmonologists.

Impact of Chronic Bronchial Infection by Staphylococcus aureus on Bronchiectasis.

The objective of the study was to analyze the factors associated with chronic bronchial infection (CBI) due to methicillin-susceptible Staphylococcus aureus (SA) and assess the clinical impact on severity, exacerbations, hospitalizations, and loss of lung function compared to patients with no isolation of PPMs in a large longitudinal series of patients from the Spanish bronchiectasis registry (RIBRON). Material and methods: A prospective, longitudinal, multicenter study was conducted with patients included in the RIBRON registry between January 2015 and October 2020. The inclusion criteria were an age of 18 years or older and an initial diagnosis of bronchiectasis. Patients recorded in the registry had a situation of clinical stability in the absence of an exacerbation in the four weeks before their inclusion. All patients were encouraged to provide a sputum sample at each visit for microbiological culture. Annual pulmonary function tests were performed according to the national spirometry guidelines. Results: A total of 426 patients were ultimately included in the study: 77 patients (18%) with CBI due to SA and 349 (82%) who did not present any isolation of PPMs in sputum. The mean age was 66.9 years (16.2), and patients 297 (69.7%) were female, with an average BMI of 25.1 (4.7) kg/m2 and an average Charlson index of 1.74 (1.33). The mean baseline value of FEV1 2 L was 0.76, with a mean FEV1% of 78.8% (23.1). One hundred and seventy-two patients (40.4%) had airflow obstruction with FEV1/FVC < 0.7. The mean predictive FACED score was 1.62 (1.41), with a mean value of 2.62 (2.07) for the EFACED score and 7.3 (4.5) for the BSI score. Patients with CBI caused by SA were younger (p < 0.0001), and they had a lower BMI (p = 0.024) and more exacerbations in the previous year (p = 0.019), as well as in the first, second, and third years of follow-up (p = 0.020, p = 0.001, and p = 0.018, respectively). As regards lung function, patients with CBI due to SA had lower levels of FEV1% at the time of inclusion in the registry (p = 0.021), and they presented more frequently with bronchial obstruction (p = 0.042). A lower age (OR: 0.97; 95% CI: 0.94–0.99; p < 0.001), lower FEV1 value% (OR: 0.98; 95% CI: 0.97–0.99; p = 0.035), higher number of affected lobes (OR: 1.53; 95% CI: 1.2–1.95; p < 0.001), and the presence of two or more exacerbations in the previous year (OR: 2.33; 95% CI: 1.15–4.69; p = 0.018) were observed as independent factors associated with CBI due to SA. The reduction in FEv1% in all patients included in the study was −0.31%/year (95% CI: −0.7; −0.07) (p = 0.110). When the reduction in FEv1% is analyzed in the group of patients with CBI due to SA and the group without pathogens, we observed that the reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in the first group and −0.02% (95% CI: −0.07, −0.01) (p = 0.918) in the second group. According to a linear regression model (mixed effects) applied to determine which factors were associated with a more pronounced reduction in FEv1% in the overall group (including those with CBI due to SA and those with no PPM isolation), age (p = 0.0019), use of inhaled corticosteroids (p = 0.004), presence of CBI due to SA (p = 0.007), female gender (p < 0.001), and the initial value of FEV1 (p < 0.001) were significantly related. Conclusions: Patients with non-CF bronchiectasis with CBI due to SA were younger, with lower FEV1% values, more significant extension of bronchiectasis, and a higher number of exacerbations of mild to moderate symptoms than those with no PPM isolation in respiratory secretions. The reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in patients with CBI caused by SA.

Chronic Bronchial Infection Is Associated with More Rapid Lung Function Decline in Chronic Obstructive Pulmonary Disease.

Rationale: Some patients with chronic obstructive pulmonary disease (COPD) suffer accelerated lung function (forced expiratory volume in 1 second [FEV1]) decline over time. Objectives: To investigate the relationship between chronic bronchial infection (CBI) and, in particular, the isolation of Pseudomonas aeruginosa (PA), and FEV1 decline in COPD. Methods: Post-hoc analysis of a prospective cohort of 201 patients with COPD followed up every 3-6 months for 84 months. CBI was defined as ⩾3 sputum positive cultures of the same pathogenic micro-organism (PPM) over 1 year. Patients were stratified according to the presence of CBI by any PPM, as well by a single or multiple isolation of PA during follow-up. An adjusted mixed-effects linear regression model was used to investigate the independent effects of CBI and PA isolation on FEV1 decline over time. Results: During follow-up, PPMs were never isolated in 43.3% of patients, in 23.9% of them PPMs were isolated once, and CBI by any PPM was confirmed in 32.8% of participants. FEV1 decline in the entire cohort was 33.7 (95% confidence interval [CI], 21.4-46.1) ml/year. This was significantly increased in patients with CBI by any PPM (57.1 [95% CI, 28.5-79.3] ml/year) and in those in whom PA was isolated at least once (48.5 [95% CI, 27.3-88.2] ml/year). Multivariable analysis showed that the presence of both CBI by any PPM, and at least one PA isolation, were independent factors associated with faster FEV1 decline adjusted by baseline FEV1, presence of bronchiectasis, body mass index, age, exacerbations, smoking status, symptoms, baseline treatment, and comorbidities. Conclusions: The presence of CBI by any PPM, and one or more PA isolation, were independently associated with FEV1 decline in patients with COPD.

The Impact of Chronic Bronchial Infection in COPD: A Proposal for Management.

Up to 50% of patients with chronic obstructive pulmonary disease (COPD) in stable state may carry potentially pathogenic microorganisms (PPMs) in their airways. The presence of PPMs has been associated with increased symptoms, increased risk and severity of exacerbations, a faster decline in lung function and impairment in quality of life. Although some clinical trials have demonstrated a reduction in exacerbations in patients chronically treated with systemic antibiotics, particularly macrolides, the selection of patients was based on the previous frequency of exacerbations and not on the presence of PPMs in their airways. Therefore, unlike in bronchiectasis, there is a lack of evidence-based recommendations for assessment and treatment of the presence of PPMs in either single or repeated isolations in COPD. In this article, we propose that chronic bronchial infection (CBI) in COPD be defined as the isolation of the same PPM in at least three sputum samples separated by more than one month; we review the impact of CBI on the natural course of COPD and suggest a course of action in patients with a single isolation of a PPM or suspected CBI. Antibiotic treatment in stable COPD should be recommended based on four main criteria: a) the presence of comorbid bronchiectasis, b) the demonstration of a single or multiple isolation of the same PPM, c) the clinical impact of CBI on the patients, and d) the type of PPM, either Pseudomonas aeruginosa or non-pseudomonal PPM. These recommendations are derived from evidence generated in patients with bronchiectasis and, until new evidence specifically obtained in COPD is available, they may help in the management of these challenging patients with COPD. Existing evidence suggests that inhaled therapy is insufficient to manage patients with moderate-to-severe COPD, frequent exacerbations, and CBI. New studies must be conducted in this particularly demanding population.

Long-Term Risk of Mortality Associated with Isolation of Pseudomonas aeruginosa in COPD: A Systematic Review and Meta-Analysis.

BackgroundChronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular Pseudomonas aeruginosa (PA) in respiratory samples on the prognosis of COPD is unclear.MethodsWe conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible.ResultsOf 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low).ConclusionThere is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.

Chronic bronchial infection and incident cardiovascular events in chronic obstructive pulmonary disease patients: A long-term observational study.

Cardiovascular (CV) diseases are frequent in patients with chronic obstructive pulmonary disease (COPD). Likewise, chronic bronchial infection (CBI) is also frequent in COPD and it is associated with systemic inflammation, a well-known CV risk factor. The objective of this study was to investigate the relationship between CBI, systemic inflammation and incident CV events. A post hoc analysis of prospectively collected cohort of 201 COPD patients [Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV] followed up every 3-6months for 84 months was conducted. CBI was defined as ≥3 positive pathogenic microorganisms sputum cultures over 1year, separated by ≥3months. Systemic inflammation was assessed by circulating levels of C-reactive protein and fibrinogen. Fatal and non-fatal CV events, including coronary and cerebrovascular events as well as arrhythmia episodes, were prospectively recorded. For analysis, they were analysed separately and combined in a composite variable. As hypothesized, CBI was associated with persistent systemic inflammation and a significantly higher incidence of CV events (HR: 3.88; 95% CI: 1.83-8.22), mainly of coronary origin independent of age, number and severity of exacerbations, comorbidities, other CV risk factors, lung function, BMI, smoking status and treatments. These associations were particularly significant in patients with CBI by Pseudomonas aeruginosa (PA). CBI, particularly by PA, is associated with sustained and enhanced systemic inflammation and a higher incidence of CV events (especially coronary events). The possibility that treating CBI may decrease systemic inflammation and CV events in COPD deserves prospective, interventional studies.

Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

BackgroundInhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations. MethodsWe performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154. ResultsTwelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70–5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81–18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28–1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82–0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35–3.27) at the end of therapy, with a number needed to treat of 6. ConclusionsIA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.

Effectiveness and Safety of Inhaled Antibiotics in Patients With Chronic Obstructive Pulmonary Disease. A Multicentre Observational Study

BackgroundWe aimed to describe the effectiveness and safety of inhaled antibiotics in chronic obstructive pulmonary disease (COPD) patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment. MethodsMulticentre retrospective observational cohort study in COPD patients who had received ≥1 dose of inhaled antibiotics in the last 5 years. Clinical data from the two years prior to and subsequent to the start of the treatment were compared. Primary outcome: COPD exacerbations. Secondary outcomes: side effects, symptomatology (sputum purulence, dyspnoea), microbiological profile and pathogen eradication. ResultsOf 693 COPD patients analyzed (aged 74.1; 86.3% men; mean FEV1=43.7%), 71.7% had bronchiectasis and 46.6% presented chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). After 1 year of treatment with inhaled antibiotics, there was a significant decrease in the number of exacerbations (−33.3%; P<.001), hospital admissions (−33.3%; P<.001) and hospitalization days (−26.2%; P=.003). We found no difference in effectiveness between patients with or without associated bronchiectasis. Positive patient outcomes were more pronounced in PA-eradicated patients. We found a significant reduction in daily expectoration (−33.1%; P=.024), mucopurulent/purulent sputum (−53.9%; P<.001), isolation of any potentially pathogenic microorganisms (PPM) (−16.7%; P<.001), CBI by any PPM (−37.4%; P<.001) and CBI by PA (−49.8%; P<.001). CBI by any PPM and ≥three previous exacerbations were associated with a better treatment response. 25.4% of patients presented non-severe side-effects, the most frequent of these being bronchospasm (10.5%), dyspnoea (8.8%) and cough (1.7%). ConclusionsIn COPD patients with multiple exacerbations and/or CBI by any PPM (especially PA), inhaled antibiotics appear to be an effective and safe treatment, regardless of the presence of bronchiectasis.

Impact of Pseudomonas aeruginosa Infection on Patients with Chronic Inflammatory Airway Diseases.

Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous and opportunistic microorganism and is considered one of the most significant pathogens that produce chronic colonization and infection of the lower respiratory tract, especially in people with chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. From a microbiological viewpoint, the presence and persistence of P. aeruginosa over time are characterized by adaptation within the host that precludes any rapid, devastating injury to the host. Moreover, this microorganism usually develops antibiotic resistance, which is accelerated in chronic infections especially in those situations where the frequent use of antimicrobials facilitates the selection of “hypermutator P. aeruginosa strain”. This phenomenon has been observed in people with bronchiectasis, CF, and the “exacerbator” COPD phenotype. From a clinical point of view, a chronic bronchial infection of P. aeruginosa has been related to more severity and poor prognosis in people with CF, bronchiectasis, and probably in COPD, but little is known on the effect of this microorganism infection in people with asthma. The relationship between the impact and treatment of P. aeruginosa infection in people with airway diseases emerges as an important future challenge and it is the most important objective of this review.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.