Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial.

IMPORTANCE: More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) treatment on blood pressure in patients with resistant hypertension. OBJECTIVE: To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS: CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES: The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS: A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg [95% CI, 0.6 to 5.6]; P = .02) and 24-hour DBP (3.2 mm Hg [95% CI, 1.0 to 5.4]; P = .005), but not in 24-hour SBP (3.1 mm Hg [95% CI, -0.6 to 6.7]; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio [OR], 2.4 [95% CI, 1.2 to 5.1]; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE: Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00616265.

Validation of a Pathological Score for the Assessment of Bronchial Biopsies in Severe Uncontrolled Asthma: Beyond Blood Eosinophils.

BACKGROUND: Blood eosinophil count (BEC) is currently used as a surrogate marker of T2 inflammation in severe asthma but its relationship with tissue T2-related changes is elusive. Bronchial biopsy could add reliable information but lacks standardization. OBJECTIVES: To validate a systematic assessment of the bronchial biopsy for the evaluation of severe uncontrolled asthma (SUA) by standardizing a pathological score. METHODS: A systematic assessment of submucosal inflammation, tissue eosinophilic count/field (TEC), goblet cells hyperplasia, epithelial changes, basement membrane thickening, prominent airway smooth muscle and submucosal mucous glands was initially agreed and validated in representative bronchial biopsies of 12 patients with SUA by 8 independent pathologists. In a second phase, 62 patients with SUA who were divided according to BEC≥300cells/mm3 or less underwent bronchoscopy with bronchial biopsies and the correlations between the pathological findings and the clinical characteristics were investigated. RESULTS: The score yielded good agreement among pathologists regarding submucosal eosinophilia, TEC, goblet cells hyperplasia and mucosal glands (ICC=0.85, 0.81, 0.85 and 0.87 respectively). There was a statistically significant correlation between BEC and TEC (r=0.393, p=0.005) that disappeared after correction by oral corticosteroids (OCS) use (r=0.170, p=0.307). However, there was statistically significant correlation between FeNO and TEC (r=0.481, p=0.006) that was maintained after correction to OCS use (r=0.419, p=0.021). 82.4% of low-BEC had submucosal eosinophilia, 50% of them moderate to severe. CONCLUSION: A standardized assessment of endobronchial biopsy is feasible and could be useful for a better phenotyping of SUA especially in those receiving OCS.

Redefining the Role of Bronchoscopy in the Workup of Severe Uncontrolled Asthma in the Era of Biologics: A Prospective Study.

BACKGROUND: Severe uncontrolled asthma (SUA) is frequently treated with biologic therapy if a T2 phenotype is found. Bronchoscopy is not routinely recommended in these patients unless a specific indication to rule out comorbidities is present. RESEARCH QUESTION: Is routine bronchoscopy safe and useful in phenotyping and endotyping patients with SUA before the indication of a biologic therapy? STUDY DESIGN AND METHODS: Prospective study of consecutive patients with SUA who were referred to a specialized asthma clinic to assess the indication of a biologic therapy. Patients were clinically phenotyped as T2-allergic, T2-eosinophilic, and non-T2. All patients underwent bronchoscopy, and systematic data collection of endoscopic findings, microbiology of bronchial aspirate, and presence of eosinophils in bronchial biopsy were recorded and compared between asthma phenotypes. Cluster analysis was performed accordingly. RESULTS: One hundred patients were recruited and classified as T2-allergic (28%), T2-eosinophilic (64%), and non-T2 (8%). On bronchoscopy, signs of gastroesophageal reflux disease were detected in 21%, vocal cord dysfunction in 5%, and tracheal abnormalities in 3%. Bronchial aspirate culture isolated bacteria in 27% of patients and fungi in 14%. Three clusters were identified: nonspecific, upper airway, and infection, the latter being less frequently associated with submucosal eosinophilia. Eosinophils were detected in 91% of bronchial biopsies. Despite a correlation to blood eosinophils, five patients with T2-phenotypes showed no eosinophils in bronchial biopsy, and three patients with non-T2 showed eosinophils in bronchial biopsy. Only one patient had moderate bleeding. INTERPRETATION: Routine bronchoscopy in SUA eligible for biologic therapy is a safe procedure that can help to better phenotype and personalize asthma management.

[Clinical utility of transbronchial needle aspiration of mediastinal lymph nodes in the diagnosis of sarcoidosis in stages I and II]. / Utilidad clínica de la punción transbronquial de adenopatías mediastínicas en el diagnóstico de la sarcoidosis en estadios I y II.

OBJECTIVE: To analyze the individual and combined diagnostic yield and clinical utility of transbronchial needle aspiration and transbronchial biopsy in the histologic diagnosis of sarcoidosis in stages I and II. PATIENTS AND METHODS: We performed a prospective study enrolling all the patients admitted to our hospital between July 2001 and June 2006 with mediastinal lymph nodes of a diameter of over 10 mm and clinical and radiological indication of sarcoidosis. The patients underwent the following tests in the order specified: a transbronchial needle aspiration of 1 or more lymph nodes using a 19-gauge histology needle until 2 satisfactory specimens were obtained, a bronchoalveolar lavage, and 4 to 6 transbronchial biopsies. RESULTS: A total of 32 patients were enrolled during the study period. Of these, 26 were finally diagnosed with sarcoidosis. The mean (SD) age of the patients was 38.9 (10.6) years and there were 13 women (50%). The mean (SD) lymph node diameter was 23.5 (6.5) mm. The most common lymph node aspiration sites were the subcarinal station (9 patients, 34.6%) and a combination of the subcarinal and paratracheal stations (7 patients, 26.9%). Computed tomography scans of the chest revealed parenchymal involvement in 12 (46.2%) patients. Fifteen (57.7%) patients were diagnosed by transbronchial biopsy and 16 (61.5%) by transbronchial needle aspiration. These techniques were used in isolation in 7 (26.9%) and 8 (30.8%) patients, respectively (P>.05). Diagnosis was achieved with the combined results of transbronchial biopsy and needle aspiration in 23 (88.4%) patients. Overall, the diagnostic yield of the combined techniques was significantly higher than that of either one in isolation (P=.01 vs transbronchial biopsy and P=.02 vs needle aspiration). In patients with parenchymal involvement, yield was better for the combined techniques only in comparison with transbronchial biopsy (P=.01). Only 4 (15%) patients developed complications and 20 (76.9%) tolerated the procedures well. CONCLUSIONS: Diagnostic yield was significantly higher when transbronchial biopsy and transbronchial needle aspiration were used in combination than when used alone, particularly in patients without parenchymal involvement. There were few complications and tolerance was good.

[Effect of different bronchial washing sequences on diagnostic yield in endoscopically visible lung cancer]. / Influencia en la rentabilidad diagnóstica del momento de realización del aspirado bronquial en los carcinomas broncogénicos endoscópicamente visibles.

OBJECTIVE: Aspiration of bronchial wash fluid is commonly used in conjunction with brushing and forceps biopsy to diagnose endoscopically visible lung cancer. However, the optimal sequence of these procedures is subject to debate. The objective of this study was to determine if the order in which bronchial washing is performed relative to bronchial brushing and forceps biopsy has any effect on the diagnostic yield. PATIENTS AND METHODS: A prospective, cross-sectional study was carried out on patients with endoscopically visible lung cancer who underwent video-assisted fiberoptic bronchoscopy for diagnostic purposes. Aspiration of bronchial wash fluid was performed on all patients both before and after bronchial brushing and forceps biopsy. The results were analyzed separately for each type of endobronchial lesion and for both together. RESULTS: The study included 75 patients, with a mean age of 63.3 years; 81% were men. Bronchoscopy was diagnostic in 71 (94.7%) cases. Findings from bronchial washing fluid were positive in 40 (53.3%) patients when washing was performed prior to brushing and forceps biopsy; when washing was performed after these procedures, findings were positive in 43 (57.3%) patients (P=.6). The combined diagnostic yield of washing before and after brushing and forceps biopsy was 69.3%, a significantly better result than either washing before (P=.001) or after (P=.004) the other sampling techniques. In cases where findings from washing done after brushing and forceps biopsy were negative (14 of 32, 43.7%), blood in the aspirated sample interfered with cytology. In comparison, when washing was performed prior to brushing and biopsy, that problem arose in only 3 of the 35 cases (8.5%) (P=.002). CONCLUSIONS: The order in which bronchial washing is performed in relation to other sampling techniques for diagnosing bronchial tumors does not influence the diagnostic yield. This is probably because the aspirated fluid sample is more likely to contain excessive blood when washing is performed after brushing and forceps biopsy. However, the diagnostic yield can be significantly increased by combining the findings from bronchial washings performed both before and after other sample collection procedures.

Isoniazid hepatotoxicity among drug users: the role of hepatitis C.

The incidence of and risk factors associated with hepatotoxicity in patients with chronic hepatitis have not been systematically studied. Therefore, we conducted a prospective study that included former drug users who were treated with isoniazid for latent tuberculosis infection. Of 415 patients, 20 (4.8%; 95% confidence interval [CI], 3-7.4) had hepatotoxicity diagnosed, and 6 (1.4%; 95% CI, 0.5-3.2) developed clinical hepatitis, none of whom had serious symptoms. The only 2 factors independently associated with isoniazid hepatotoxicity were excessive alcohol consumption (odds ratio [OR]; 4.2, 95% CI, 1.6-10.8; P=.002) and a high baseline alanine transaminase level (OR, 4.3; 95% CI, 1.6-11.4; P=.002). The presence of hepatitis C virus antibodies was associated with hepatotoxicity only on univariate analysis. Treatment with isoniazid in drug users appears to be safe and well tolerated, although frequent asymptomatic elevations in transaminase levels were observed.

[Sleep apnoea in patients of elderly: care activity in Spain (2002-2008)]. / Apnea del sueño en individuos de edad avanzada. Actividad asistencial (2002-2008) en España.

INTRODUCTION AND OBJECTIVE: There is a significant lack of scientific evidence on the role of SAHS in the elderly despite the increasing ageing of the population. The objective of the present study is to analyse the current healthcare situation in Spain on the diagnosis and treatment of sleep apnea in the population ≥65 years and its progress over the last few years. MATERIAL AND METHOD: Cross-sectional study. Healthcare information was collected on the diagnosis and treatment of patients of both sexes and ≥65 years suspected with having SAHS and referred to sleep units (SU) between 2002 and 2008. RESULTS: There were 51,229 sleep studies performed in 16 SU. Of these, 24.3% were performed on subjects ≥ 65 years (64.9% males), of which 71.5% had an AHI (apnoea-hypopnoea index) >10 (68.6% treated with CPAP). There were no differences over time as regards mean age, mean AHI or percentage of studies done. A significant decrease was observed in the number of CPAP prescribed to males ≥65 years from 2002 to 2005 (p=0.01) which subsequently increased up to 2008 (p=0.01). This phenomenon was not observed in women ≥65 years. CONCLUSION: Despite the lack of evidence on the subject, healthcare activity due to suspected SAHS in the elderly population is intense, therefore it should be a priority to start clinical studies that may be able to answer key questions on the diagnosis and treatment of SAHS in this age group.