Efficacy, results, and complications of mechanical ventilation in children with status asthmaticus.

We have conducted a retrospective survey of 79 children out of a total hospital asthmatic patient population of 2,412, admitted over a 32 month period to the ICU for the management of severe status asthmaticus. All patients were in severe respiratory distress with CO2 retention; 19 required mechanical ventilation due to increasing fatigue and worsening bronchospasm, having failed to respond to either inhaled or IV bronchodilator therapy. All patients were ventilated at slow rates (less than 12 min) and their airway pressure (Paw) was deliberately kept below 45 cmH2O, while accepting a PaCO2 in the 45-60 mmHg range, as long as the pH was compensated. Although two patients developed pneumothoraces while on positive pressure ventilation, these were resolved without incidents. Five patients who had mediastinal or subcutaneous air leaks prior to intubation did not develop pneumothoraces. Following the initiation of mechanical ventilation, IV beta-agonist therapy was increased in order to reverse the bronchospasm and reduce the duration of mechanical ventilation. Mean duration of intubation was 42 hours. Fourteen of the 19 patients were weaned and extubated within 48 hours. All patients survived without sequelae. We conclude that a degree of controlled "hypoventilation" by deliberately choosing Paw less than 45 cmH2O can be successfully used to ventilate children with severe status asthmaticus with a reduced rate of pressure-related complications.     

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??Abstract??Wheeze is a common symptom in infants and pre-school children characterized by chronic inflammation of the airway. The management of infantile wheeze focuses on anti-inflammatory agents including corticosteroids?? bronchodilators?? leukotriene receptor antagonists?? antihistamine drugs and macrolides. Here we reviewed the current medications of infantile wheeze and propose a de-escalation combined therapy based on our long-term practice.     

Survey to determine the efficacy and safety of guideline-based pharmacological therapy for chronic obstructive pulmonary disease patients not previously receiving maintenance treatment

Objective: To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment.

Research design and methods: Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 70%; predicted FEV₁ < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48.

Main outcome measures: The primary endpoint was change in pulmonary function (trough FEV₁, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy.

Results: Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV₁ and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved.

Conclusions: Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines.     

New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives Dave Singh

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β₂-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV₁), although the FEV₁ improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV₁ and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.     

双水平气道正压通气联合雾化吸入治疗AECOPD临床研究

目的探讨双水平气道正压通气(BiPAP)呼吸机加雾化吸入复方异丙托溴铵溶液治疗慢性阻塞性肺疾病急性加重(AECOPD)的临床疗效。方法 96例AECOPD患者随机分为治疗组和对照组。两组患者均根据痰培养及药敏结果选用敏感抗生素,纠正酸碱失衡及水、电解质紊乱,给予解痉平喘、止咳祛痰及营养支持等常规治疗,并使用BiPAP呼吸机治疗。治疗组在此基础上加用复方异丙托溴铵溶液2 ml(含异丙托溴铵4 mg,沙丁胺醇2 mg)加生理盐水3 ml雾化吸入15~20 min,2次/d。结果 1治疗组总有效率为91.7%(44/48),对照组总有效率为81.3%(39/48),两组比较差异有统计学意义(P0.05);2治疗组死亡1例,对照组死亡3例,两组对比差异无统计学意义(P0.05)。3治疗后两组动脉血二氧化碳分压逐渐下降,治疗组下降更明显,两组比较差异均有统计学意义(P0.01)。治疗后两组动脉血氧分压、pH、动脉血氧饱和度逐渐升高,治疗组升高更明显,两组比较差异均有统计学意义(P0.05或P0.01)。4治疗后两组心率、呼吸频率逐渐下降,治疗组下降更明显,两组比较差异均有统计学意义(P0.05或P0.01)。5治疗组与对照组通气时间、住院天数比较差异有统计学意义(P0.01),治疗组通气时间、住院天数均比对照组缩短。结论 BiPAP联合雾化吸入复方异丙托溴铵溶液治疗AECOPD具有疗效显著、操作简单、安全方便等优点,值得在临床推广应用。     

Reduction in Hospital Readmission Rates Among Medicare Beneficiaries With Chronic Obstructive Pulmonary Disease: A Real-world Outcomes Study of Nebulized Bronchodilators

PurposeChronic obstructive pulmonary disease (COPD) is a common condition responsible for substantial morbidity, mortality, and costs in the United States. The economic burden of COPD is driven primarily by hospitalizations, with 1 in 5 hospitalized patients experiencing a 30-day readmission. Bronchodilators, delivered via handheld inhalers or nebulizers, are the mainstay of therapy for COPD. However, differences in outcomes between short- and long-acting therapies are unclear. We examined real-world differences in 30-day readmission and exacerbation rates between Medicare beneficiaries with COPD treated with a nebulized long-acting beta₂-agonist (arformoterol tartrate [ARF]) and beneficiaries treated with a nebulized short-acting beta₂-agonist (SABA) for maintenance therapy after hospital discharge.MethodsTruven MarketScan Hospital Drug Database and Medicare files were probabilistically matched between 2009 and 2013 to identify beneficiaries who were aged ≥65 years and discharged from a hospital with a primary COPD diagnosis or a secondary COPD diagnosis and a primary diagnosis for another respiratory condition. Matching was performed by using COPD hospitalization date (±7 days) and source, length of stay (±1 day), discharge date and destination, and hospital region. After applying additional inclusion/exclusion criteria, 2 cohorts were created: nebulized ARF users (n = 953) and nebulized SABA users (n = 6939). Logistic regression analyses were used to examine 30-day readmission (all-cause and COPD related) and exacerbation rates. Odds ratios (ORs), 95% CIs, and P values were computed.FindingsOn average, nebulized SABA users had more comorbidities than nebulized ARF users, including diabetes, atrial fibrillation, renal disease, musculoskeletal disease, myocardial infarction, and cognitive impairment (all, P < 0.0001). However, nebulized ARF users had a higher average COPD severity score than nebulized SABA users (49.5 v. 38.0; P < 0.001). COPD therapies at baseline were similar in both cohorts and included systemic corticosteroids (≥65%), short-acting bronchodilators (≥33%), and inhaled corticosteroids + long-acting beta₂-agonists (30%). After adjusting for sociodemographic and hospital characteristics, concomitant medications, and case-mix, nebulized ARF users had 27% lower odds of an all-cause readmission (OR, 0.73; 95% CI, 0.59–0.92; P = 0.008) and 23% lower odds of a COPD-related readmission (OR, 0.77; 95% CI, 0.60–0.98; P = 0.032) at 30 days compared with users of a nebulized SABA. No difference was found in 30-day exacerbation rates between the cohorts.ImplicationsNebulized ARF users had lower 30-day readmission rates, greater COPD severity, and fewer comorbidities than nebulized SABA users. In this population, maintenance treatment with ARF reduced costly COPD outcomes.     

Triple Therapy in COPD: What We Know and What We Don't

Triple inhaled therapy for chronic obstructive pulmonary disease (COPD) consists of an inhaled corticosteroid (ICS), a long-acting β₂-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) taken in combination. Triple therapy is recommended by the Global initiative for Chronic Obstructive Lung Disease (GOLD) for patients who experience recurrent exacerbations despite treatment with either a dual bronchodilator (preferred initial therapy) or LABA/ICS combination (alternative initial therapy). Although there is evidence for the greater efficacy of triple therapy compared with LABA/ICS and LAMA monotherapy with regards to improved lung function, health status, and exacerbation rate, the efficacy of triple therapy when compared with dual bronchodilation (LABA/LAMA) is as yet unknown. As ICS use is associated with an increased risk of developing pneumonia, it is important to assess the risk/benefit ratio of triple therapy on an individual basis, and identify patients most likely to benefit. The role of elevated blood eosinophils as a biomarker for the identification of candidates for ICS treatment is currently debated, and further prospective evidence is required. This review assesses evidence for the efficacy and safety of triple therapy and postulates on the prospective evidence from ongoing studies. The potential for treating patients who experience further exacerbations on dual bronchodilation according to phenotype is also considered, as well as withdrawal of ICS from triple therapy in patients who are unlikely to benefit.