Effect of continuous positive airway pressure treatment on permeability, inflammation and mucus production of human epithelial cells.
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ABSTRACT:
SUBMITTER: Grau-Bartual S
PROVIDER: S-EPMC7276533 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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Project description:The treatment of choice for obstructive sleep apnoea (OSA) is continuous positive airway pressure therapy (CPAP). Since its introduction in clinical practice, CPAP has been used in various clinical conditions with variable and heterogeneous outcomes. In addition to the well-known effects on the upper airway CPAP impacts on intrathoracic pressures, haemodynamics and blood pressure (BP) control. However, short- and long-term effects of CPAP therapy depend on multiple variables which include symptoms, underlying condition, pressure used, treatment acceptance, compliance and usage. CPAP can alter long-term cardiovascular risk in patients with cardiorespiratory conditions. Furthermore, the effect of CPAP on the awake patient differs from the effect on the patients while asleep, and this might contribute to discomfort and removal of the use interface. The purpose of this review is to highlight the physiological impact of CPAP on the cardiorespiratory system, including short-term benefits and long-term outcomes.
| S-EPMC5803058 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is a common risk factor for cardiovascular disease. Continuous positive airway pressure (CPAP) improves OSA symptoms and blood pressure (BP) control. The effect of CPAP on BP variability (BPV) in patients with and without hypertension treated with autotitrating CPAP (APAP) for 2 weeks was studied. A total of 78 participants (76.9% men, 49% hypertensive, mean body mass index 36.2 [6.9] kg/m2 , age 49.0 [12.9] years) underwent 2 weeks of APAP therapy. Office BP, BPV (standard deviation of three BP measurements), and pulse rate were measured before and after treatment. Systolic BPV (5.3±4.9 vs 4.2±3.4 mm Hg, P=.047) and pulse rate (78.0±14.5 vs 75.5±15.8 beats per minute, P=.032) decreased after treatment, particularly in hypertensive participants. Mask leak was independently associated with reduced changes in systolic BPV (r=-0.237, P=.048). Short-term APAP treatment reduced BPV and pulse rate, particularly in hypertensive patients with OSA.
| S-EPMC8031566 | biostudies-literature
Project description:IL-13-induced goblet cell metaplasia contributes to airway remodeling and pathological mucus hypersecretion in asthma. miRNAs are potent modulators of cellular responses, but their role in mucus regulation is largely unexplored. We hypothesized that airway epithelial miRNAs play roles in IL-13-induced mucus regulation. miR-141 is highly expressed in human and mouse airway epithelium, is altered in bronchial brushings from asthmatic subjects at baseline, and is induced shortly after airway allergen exposure. We established a CRISPR/Cas9-based protocol to target miR-141 in primary human bronchial epithelial cells that were differentiated at air-liquid-interface, and goblet cell hyperplasia was induced by IL-13 stimulation. miR-141 disruption resulted in decreased goblet cell frequency, intracellular MUC5AC, and total secreted mucus. These effects correlated with a reduction in a goblet cell gene expression signature and enrichment of a basal cell gene expression signature defined by single cell RNA sequencing. Furthermore, intranasal administration of a sequence-specific mmu-miR-141-3p inhibitor in mice decreased Aspergillus-induced secreted mucus and mucus-producing cells in the lung and reduced airway hyperresponsiveness without affecting cellular inflammation. In conclusion, we have identified a miRNA that regulates pathological airway mucus production and is amenable to therapeutic manipulation through an inhaled route.
| S-EPMC8021117 | biostudies-literature
Project description:RationaleStudies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity.ObjectivesTo evaluate whether nocturnal CPAP decreased the provocative concentration of methacholine to reduce FEV1 by 20% (PC20).MethodsOne hundred ninety-four individuals with asthma were randomized (1:1:1) to use CPAP with warmed, filtered, humidified air at night at pressures either less than 1 cm H2O (sham) or at 5 cm H2O or 10 cm H2O. The primary outcome was change in PC20 after 12 weeks.Measurements and main resultsAdherence to CPAP was low in all groups. Regardless, all groups had a significant improvement in PC20, with 12 weeks/baseline PC20 ratios of 2.12, 1.73, and 1.78 for the sham, 5 cm H2O, and 10 cm H2O groups, respectively, and no significant differences between the active and sham groups. Changes in FEV1 and exhaled nitric oxide were minimal in all groups. The sham group had larger improvements in most patient-reported outcomes measuring asthma symptoms and quality of life, as well as sinus symptoms, than the 5 cm H2O group. The 10 cm H2O group showed similar but less consistent improvements in scores, which were not different from improvements in the sham group.ConclusionsAdherence to nocturnal CPAP was low. There was no evidence to support positive pressure as being effective for reducing airway reactivity in people with well-controlled asthma. Regardless, airway reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airway reactivity. Clinical trial registered with www.clinicaltrials.gov (NCT01629823).
| S-EPMC5122477 | biostudies-literature
Project description:Obstructive sleep apnea (OSA) is a common disease, with approximately 3-7% of men and 2-5% of women worldwide suffering from symptomatic OSA. If OSA is left untreated, hypoxia, microarousals and increased chemoreceptor stimulation can lead to complications like hypertension (HT). Continuous positive airway pressure (CPAP) is the most common treatment for OSA, and it works by generating airway patency, which will counteract the apnea or hypopnea. More than one billion people in the world suffer from HT, and the usual treatment is pharmacological with antihypertensive medication (AHM). The focus of this review will be to investigate whether the CPAP therapy for OSA affects HT.
| S-EPMC7956605 | biostudies-literature
Project description:Common respiratory diseases continue to represent a major public health problem, and much of the morbidity and mortality is due to airway inflammation and mucus production. Previous studies indicated a role for mitogen-activated protein kinase 14 (MAPK14) in this type of disease, but clinical trials are unsuccessful to date. Our previous work identified a related but distinct kinase known as MAPK13 that is activated in respiratory airway diseases and is required for mucus production in human cell-culture models. Support for MAPK13 function in these models came from effectiveness of MAPK13 versus MAPK14 gene-knockdown and from first-generation MAPK13-14 inhibitors. However, these first-generation inhibitors were incompletely optimized for blocking activity and were untested in vivo. Here we report the next generation and selection of a potent MAPK13-14 inhibitor (designated NuP-3) that more effectively down-regulates type-2 cytokine-stimulated mucus production in air-liquid interface and organoid cultures of human airway epithelial cells. We also show that NuP-3 treatment prevents respiratory airway inflammation and mucus production in new minipig models of airway disease triggered by type-2 cytokine challenge or respiratory viral infection. The results thereby provide the next advance in developing a small-molecule kinase inhibitor to address key features of respiratory disease.
| S-EPMC10246002 | biostudies-literature
Project description:Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ?15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12?weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04?mmHg, 95% CI -4.02-?-0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54?mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90?mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12?weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment.
| S-EPMC5593343 | biostudies-other
Project description:BackgroundSleep quality could be affected by air pollution, especially for particulate matter with a diameter of less than 10 microns (PM10) and particulate matter with a diameter of less than 2.5 microns (PM2.5). However, no direct study demonstrates the relationship and impact of air pollution especially PM10 and PM2.5 on continuous positive airway pressure (CPAP) adherence. Thus, we aimed to study the correlation between PM10, PM2.5, and low CPAP adherence in subjects with obstructive sleep apnea (OSA).MethodsWe conducted a time-series study from August 2016 to May 2022 in Chiang Mai, Thailand. The data from 2,686 visits of CPAP compliance records from 839 OSA patients' electronic medical records at the Sleep Disorders Center, Center of Medical Excellence, Chiang Mai University, Chiang Mai, Thailand were reviewed. The level of adherence was determined utilizing the provided data. Low CPAP adherence was defined as using CPAP for less than 240 minutes per night or less than 70% of nights (i.e., <5 nights/week) in the previous month. The correlation between the monthly average of PM10 and PM2.5 and the rate of low CPAP adherence was analyzed using generalized linear mixed model (GLMM) after adjustment for confounding factors.ResultsThere was no effect of an increase in PM10 and PM2.5 on low CPAP adherence [adjusted risk ratio (RR) =0.97; 95% confidence interval (CI): 0.87, 1.09; P value =0.624 and adjusted RR =0.93; 95% CI: 0.81, 1.08; P value =0.350 for PM10 and PM2.5, respectively].ConclusionsThere was no effect of particulate matter on CPAP adherence in OSA patients.
| S-EPMC11009577 | biostudies-literature
Project description:PURPOSE:To determine if a real-time magnetic resonance imaging (RT-MRI) method during continuous positive airway pressure (CPAP) can be used to measure neuromuscular reflex and/or passive collapsibility of the upper airway in individual obstructive sleep apnea (OSA) subjects. MATERIALS AND METHODS:We conducted experiments on four adolescents with OSA and three healthy controls, during natural sleep and during wakefulness. Data were acquired on a clinical 3T scanner using simultaneous multislice (SMS) RT-MRI during CPAP. CPAP pressure level was alternated between therapeutic and subtherapeutic levels. Segmented airway area changes in response to rapid CPAP pressure drop and restoration were used to estimate 1) upper airway loop gain (UALG), and 2) anatomical risk factors, including fluctuation of airway area (FAA). RESULTS:FAA significantly differed between OSA patients (2-4× larger) and healthy controls (Student's t-test, P < 0.05). UALG and FAA measurements indicate that neuromuscular reflex and passive collapsibility varied among the OSA patients, suggesting the presence of different OSA phenotypes. Measurements had high intrasubject reproducibility (intraclass correlation coefficient r > 0.7). CONCLUSION:SMS RT-MRI during CPAP can reproducibly identify physiological traits and anatomical risk factors that are valuable in the assessment of OSA. This technique can potentially locate the most collapsible airway sites. Both UALG and FAA possess large variation among OSA patients. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1400-1408.
| S-EPMC5568520 | biostudies-literature
Project description:Asthma is characterised by airway hyperreactivity, which is primarily treated with ?-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8-10 cmH(2)O) or sham treatment (0-2 cmH(2)O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC(20)). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (?)logPC(20) 0.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (?logPC(20) 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (?logPC(20) 0.41, p<0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage.
| S-EPMC4727535 | biostudies-literature