The impact of smoking on bronchiectasis and its comorbidities.

INTRODUCTION: Bronchiectasis, characterized by irreversible bronchial dilatation, is a growing global health concern with significant morbidity. This review delves into the intricate relationship between smoking and bronchiectasis, examining its epidemiology, pathophysiology, clinical manifestations, and therapeutic approaches. Our comprehensive literature search on PubMed utilized MESH terms including 'smoking,' 'smoking cessation,' 'bronchiectasis,' and 'comorbidities' to gather relevant studies. AREAS COVERED: This review emphasizes the role of smoking in bronchiectasis development and exacerbation by compromising airways and immune function. Interconnected comorbidities, including chronic obstructive pulmonary disease, asthma, and gastroesophageal reflux disease, create a detrimental cycle affecting patient outcomes. Despite limited studies on smoking cessation in bronchiectasis, the review stresses its importance. Advocating for tailored cessation programs, interventions like drainage, bronchodilators, and targeted antibiotics are crucial to disrupting the inflammatory-infection-widening cycle. EXPERT OPINION: The importance of smoking cessation in bronchiectasis management is paramount due to its extensive negative impact on related conditions. Proactive cessation programs utilizing technology and targeted education for high-risk groups aim to reduce smoking's impact on disease progression and related comorbidities. In conclusion, a personalized approach centered on smoking cessation is deemed vital for bronchiectasis, aiming to improve outcomes and enhance patients' quality of life in the face of this complex respiratory condition.

[Bronchiectasis not due to cystic fibrosis]. / Bronquiectasias no debidas a fibrosis quística.

Bronchiectasis is a clinical-radiological condition composed of irreversible bronchial dilation due to inflammation and infection of the airways, which causes respiratory symptoms, usually productive cough and infectious exacerbations. Bronchiectasis can have multiple causes, both pulmonary and extrapulmonary, and its clinical presentation is very heterogenous. Its prevalence is unknown, although up to 35-50% of severe COPD and 25% of severe asthma present them, so their underdiagnosis is evident. Chronic bacterial bronchial infection is common, and Pseudomonas aeruginosa is the pathogen that has been found to imply a worse prognosis. Treatment of bronchiectasis has three fundamental characteristics: it must be multidisciplinary (involvement of several specialties), pyramidal (from primary care to the most specialized units) and multidimensional (management of all aspects that make up the disease).

Linking obstructive sleep apnoea and lung cancer: a further step down the road.

There are various pathophysiological pathways linking obstructive sleep apnoea and lung cancer https://bit.ly/48qtqOO.

Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

BACKGROUND: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored. RESEARCH QUESTION: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma? STUDY DESIGN AND METHODS: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome. RESULTS: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90). INTERPRETATION: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA.

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.

The U-Shaped Relationship Between Eosinophil Count and Bronchiectasis Severity: The Effect of Inhaled Corticosteroids.

BACKGROUND: Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis RESEARCH QUESTION: Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? STUDY DESIGN AND METHODS: This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/µL), (2) low number of eosinophils (51-100/µL), (3) normal number of eosinophils (101-300/µL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/µL). RESULTS: Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/µL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/µL, 488 patients (52.6%) with 101-300 eosinophils/µL, and 153 patients (16.5%) with > 300 eosinophils/µL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/µL. INTERPRETATION: A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group.

The role of precision medicine in bronchiectasis: emerging data and clinical implications.

INTRODUCTION: Bronchiectasis is a very heterogeneous disease. This heterogeneity has several consequences: severity cannot be measured by a single variable, so multidimensional scores have been developed to capture it more broadly. Some groups of patients with similar clinical characteristics or prognoses (clinical phenotypes), and even similar inflammatory profiles (endotypes), have been identified, and these have been shown to require a more specific treatment. AREAS COVERED: We comment on this 'stratified' model of medicine as an intermediate step toward the application of the usual concepts on which precision medicine is based (such as cellular, molecular or genetic biomarkers, treatable traits and individual clinical fingerprinting), whereby each subject presents certain specific characteristics and receives individualized treatment. EXPERT OPINION: True precision or personalized medicine is based on concepts that have not yet been fully achieved in bronchiectasis, although some authors are already beginning to adapt them to this disease in terms of pulmonary and extrapulmonary etiologies, clinical fingerprinting (specific to each individual), cellular biomarkers such as neutrophils and eosinophils (in peripheral blood) and molecular biomarkers such as neutrophil elastase. In therapeutic terms, the future is promising, and some molecules with significant antibiotic and anti-inflammatory properties are being developed.

Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer.

Several epidemiological and clinical studies have suggested a relationship between obstructive sleep apnea (OSA) and a higher incidence or severity of cancer. This relationship appears to be dependent on a myriad of factors. These include non-modifiable factors, such as age and gender; and modifiable or preventable factors, such as specific comorbidities (especially obesity), the use of particular treatments, and, above all, the histological type or location of the cancer. Heterogeneity in the relationship between OSA and cancer is also related to the influences of intermittent hypoxemia (a hallmark feature of OSA), among others, on metabolism and the microenvironment of different types of tumoral cells. The hypoxia inducible transcription factor (HIF-1α), a molecule activated and expressed in situations of hypoxemia, seems to be key to enabling a variety of pathophysiological mechanisms that are becoming increasingly better recognized. These mechanisms appear to be operationally involved via alterations in different cellular functions (mainly involving the immune system) and molecular functions, and by inducing modifications in the microbiome. This, in turn, may individually or collectively increase the risk of cancer, which is then, further modulated by the genetic susceptibility of the individual. Here, we provide an updated and brief review of the different pathophysiological pathways that have been identified and could explain the relationship between OSA and cancer. We also identify future challenges that need to be overcome in this intriguing field of research.

Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Significance and Potential Role of Eosinophils in Non-Cystic Fibrosis Bronchiectasis.

Bronchiectasis is a complex and heterogeneous disease with a myriad of pulmonary and extrapulmonary etiologies. Bronchiectasis has a predominantly neutrophilic inflammatory profile. However, eosinophilic inflammation has also been documented in both the airways and the systemic circulation. Various diseases (eg, asthma, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyps) characterized by heightened type 2 airway inflammatory responses, including blood or sputum eosinophilia, may coexist with bronchiectasis. Apart from those eosinophilic etiologies or comorbidities related to bronchiectasis, around 20% of patients with bronchiectasis have peripheral eosinophilia (at least 3% or 300 eosinophils/µL) with no identified concomitant disease (also termed "eosinophilic bronchiectasis"), whose roles have not been fully understood. The two key points regarding these observations are that eosinophils confer both bactericidal and antiviral properties against common pathogenic microorganisms that are usually detected in bronchiectasis, and that eosinophilic bronchiectasis has been associated with better therapeutic response to inhaled corticosteroids and other anti-TH2 profile treatments. In this review, we summarize the most significant evidence regarding the role of eosinophils in patients with bronchiectasis, including the association of bronchiectasis with eosinophilic diseases (as etiologies or comorbidities), and existing data on eosinophilic bronchiectasis not related to eosinophilic disorders.