Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges

Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) and refractory hypertension (RfH). Recent findings suggest that the former may be due to an alteration in the renin–angiotensin–aldosterone axis, while the latter seems to be more closely related to sympathetic hyper-activation. Both these pathophysiological mechanisms are also activated in patients with obstructive sleep apnoea (OSA). It is not surprising, therefore, that the prevalence of OSA in RH and RfH patients is very high (as reflected in several studies) and that treatment with continuous positive airway pressure (CPAP) manages to reduce blood pressure levels in a clinically significant way in both these groups of hypertensive patients. It is therefore necessary to incorporate into the multidimensional treatment of patients with RH and RfH (changes in lifestyle, control of obesity and drug treatment) a study of the possible existence of OSA, as this is a potentially treatable disease. There are many questions that remain to be answered, especially regarding the ideal combination of treatment in patients with RH/RfH and OSA (drugs, renal denervation, CPAP treatment) and patients’ varying response to CPAP treatment

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/mu L, with 27 (23.5%), 63 (54.8%), and 25 patients (21.7%) presenting, respectively, less than 100, 101-300, and more than 300 eosinophils/mu L. 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/mu L presented more infectious events (incident exacerbations, pneumonic episodes, and chronic bronchial infection via pathogenic bacteria). Only those patients with eosinophilia (>300 eosinophils/mu L) 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)

Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease

[Background]: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD.[Methods]: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment.[Results]: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3–5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1–1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02–1.3]) were independent risk factors for the progression or development of BE.[Conclusions]: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD

Etiology of Bronchiectasis in the World: Data from the Published National and International Registries

Bronchiectasis is the third leading chronic inflammatory disease of the airway caused by dozens of pulmonary and extra-pulmonary diseases. Infection by pathogenic microorganisms is very common. We aimed to analyze, for the first time in the literature, the etiology of bronchiectasis throughout the world via data published in national and international registries. A bibliographic search was carried out in PubMed and Web of Science. Seven studies were included, with a total of 27,258 patients from 33 countries of four continents. The most frequent cause of bronchiectasis was post-infectious: 30.5% (range: 19.1–40.4%), followed by idiopathic: 28.7% (18.5–38.1%). Post-tuberculous bronchiectasis accounted for 14.1% (1.8–35.5%), while etiologies associated with COPD and asthma comprised 7% (3.4–10.9%) and 5.2% (2.5–7.8%). In conclusion, there was a high degree of heterogeneity in the relative percentages of the main causes of bronchiectasis in the world, although post-infectious and idiophatic bronchiectasis continue to be the most frequent causes

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

COPD; Bronchial infection; MortalityEPOC; Infección bronquial; MortalidadMPOC; Infecció bronquial; MortalitatBackground: Chronic 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. Methods: We 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. Results: Of 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). Conclusion: There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.This study has been funded by an unrestricted grant from Boehringer Ingelheim Spain

Rationale and Clinical Use of Bronchodilators in Adults with Bronchiectasis

: Currently, there is much controversy surrounding the therapeutic approach to pulmonary function abnormalities in patients with bronchiectasis and, consequently, whether and when to use bronchodilators in these patients. National and international guidelines on the treatment of bronchiectasis in adults do not recommend the routine use of bronchodilators because there is no evidence that a significant response to a bronchodilator or the presence or hyperresponsiveness of the airway are good predictors of future effective clinical response. However, some guidelines recommend them in the presence of airway obstruction and/or special conditions, which vary according to the guideline in question, although there are no recommendations on optimal dosing and bronchodilator treatment combined with or without inhaled corticosteroids. Nonetheless, in contrast with guideline recommendations, bronchodilators are overused in real-world patients with bronchiectasis even in the absence of airway obstruction, as demonstrated by analysis of national and international registries. This overuse can be explained by the awareness of the existence of a solid pharmacological rationale that supports the use of bronchodilators in the presence of chronic airway obstruction independent of its aetiology. We performed a systematic review of the literature and were able to verify that there are no randomised controlled trials (apart from a small study with methodological limitations and a very recent trial involving a not-very-large number of patients), or any long-term observational studies on the short- or long-term effect of bronchodilators in patients with bronchiectasis. Therefore, we believe that it is essential and even urgent to evaluate the effects of bronchodilators in these patients with appropriately designed studies

Obstructive Sleep Apnea and Arterial Hypertension: Implications of Treatment Adherence

[Purpose of Review]: This review seeks to present an overview of the recent literature on the importance of CPAP and antihypertensive treatment adherence in blood pressure control of hypertensive patients, especially those with obstructive sleep apnea.[Recent Findings]: Although it is unquestionable that a good adherence to CPAP and antihypertensive drugs is crucial to improvements in sleep-related symptoms, blood pressure levels (even the modest reductions of 2–2.5 mmHg achieved by CPAP treatment) and future cardiovascular risk, this adherence decreases over time, despite efforts made toward behavioral intervention and monitoring. Curiously, although taking a drug would seem to be easier than the use of CPAP treatment, based on current information, it seems that the compliance with drug treatment in hypertensive subjects is not better than that achieved with CPAP treatment in OSA patients with hypertension. However, some studies have shown some phenotypes of hypertensive and OSA patients with good adherence and better hypertensive effect, such as those with uncontrolled blood pressure (resistant and refractory hypertension), severe forms of sleep apnea, and more sleep-related symptoms, especially a higher degree of diurnal hypersomnia.[Summary]: The positive effect of antihypertensive drugs and CPAP treatment on blood pressure levels depends on the degree of treatment adherence, especially in forms of uncontrolled hypertension, but this adherence decreases over time. Educational programs and new devices are needed to improve adherence to treatment in these patients, along with fuller understanding of the different patterns and phenotypes of non-adherence

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

Complexity and Heterogeneity in Bronchiectasis: Towards a Personalized Medicine

Bronchiectasis is a complex and heterogeneous disease, defining complexity as to the non-linear relationship between the different characteristics that make up the disease, and heterogeneous in the sense that not all these variables appear in the same patient. As a consequence of the complexity and heterogeneity of bronchiectasis, different clinical phenotypes can be established (mainly chronic bronchial infection by Pseudomonas aeruginosa, the exacerbator patient, and the overlap with chronic obstructive pulmonary disease [COPD]), as well as endotypes (basically neutrophilic and eosinophilic). Beyond phenotypes and endotypes, some authors have recently developed some tools to capture the multidimensional nature of bronchiectasis such as the control panel and clinical fingerprint. These tools are based on the concepts of severity, activity and impact of the disease. Finally, the concept of treatable trait, initially described in COPD patients and defined as those characteristics of bronchiectasis that are treatable (or potentially treatable) is discussed