Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomised controlled study.

OBJECTIVE--To examine the effect of bronchodilator treatment given continuously versus on demand on the progression of asthma and chronic bronchitis and to compare the long term effects of a beta 2 adrenergic drug (salbutamol) and an anticholinergic drug (ipratropium bromide). DESIGN--Two year randomised controlled prospective ''crossover'' study in which patients were assigned to one of two parallel treatment groups receiving continuous treatment or treatment on demand. SETTING--29 general practices in the catchment area of the University of Nijmegen. PATIENTS--223 patients aged greater than or equal to 30 with moderate airway obstruction due to asthma or chronic bronchitis, selected by their general practitioners. INTERVENTIONS--1600 micrograms salbutamol or 160 micrograms ipratropium bromide daily (113 patients) or salbutamol or ipratropium bromide only during exacerbations or periods of dyspnoea (110). No other pulmonary treatment was permitted. MAIN OUTCOME MEASURES--Decline in ventilatory function and change in bronchial responsiveness, respiratory symptoms, number of exacerbations, and quality of life. RESULTS--Among 144 patients completing the study, after correction for possible confounding factors the decline in forced expiratory volume in one second was -0.072 l/year in continuously treated patients and -0.020 l/year in those treated on demand (p less than 0.05), irrespective of the drug. The difference in the decline in patients with asthma was comparable with that in patients with chronic bronchitis (asthma: 0.092 v -0.025 l/year; chronic bronchitis: -0.082 v -0.031 l/year). Bronchial responsiveness increased slightly (0.4 doubling dose) with continuous treatment in chronic bronchitis, but exacerbations, symptoms, and quality of life were unchanged. Salbutamol and ipratropium bromide had comparable effects on all variables investigated. CONCLUSIONS--Continuous bronchodilator treatment without anti-inflammatory treatment accelerates decline in ventilatory function. Bronchodilators should be used only on demand, with additional corticosteroid treatment, if necessary.     

Respiratory symptoms as predictors of 27 year mortality in a representative sample of British adults.

OBJECTIVE--To examine associations between reported respiratory symptoms (as elicited by questionnaire) and subsequent mortality. DESIGN--Prospective cohort study. SETTING--92 General practices in Great Britain. PARTICIPANTS--A nationally representative sample of 1532 British men and women aged between 40 and 64. MAIN OUTCOME MEASURES--Mortality from all causes, cardiovascular disease, lung cancer, and chronic bronchitis. RESULTS--Subjects were interviewed in 1958 regarding various respiratory symptoms (including cough, phlegm, breathlessness, and wheeze) by using a questionnaire which formed the basis of the Medical Research Council''s questionnaire on respiratory symptoms. By the end of 1985, 889 deaths had been reported, including 51 in men due to chronic bronchitis. After adjustment for differences in age and smoking habits death rates from chronic bronchitis in men who reported symptoms were greater than those in men who did not for each of the symptoms examined. The adjusted mortality ratios were 3.4 (95% confidence interval 1.8 to 6.5) for morning cough, 3.7 (2.0 to 6.9) for morning phlegm, 6.4 (3.0 to 13.8) for breathlessness when walking on the level, and 10.5 (4.4 to 24.6) for wheeze most days or nights. Mortality ratios were also significantly raised for four episodic symptoms not usually included in more recent respiratory symptom questionnaires--namely, occasional wheeze (mortality ratio 6.0; 95% confidence interval, 2.4 to 15.1), weather affects chest (5.7; 3.1 to 10.3), breathing different in summer (4.9; 2.8 to 8.6), and cold usually goes to chest (3.7; 2.0 to 6.8). The excess mortality associated with these symptoms remained significant after further adjustment for breathlessness or phlegm. Ratios for all cause mortality in men and women were also significantly raised for most respiratory symptoms, death rates being some 20-50% higher in people reporting symptoms after adjustment for age, sex, and smoking. Breathlessness was the only symptom significantly associated with excess mortality from cardiovascular disease (mortality ratio 1.4 (95% confidence interval 1.0 to 1.9) for breathlessness when walking on the level). Ratios were generally around unity and not significant for mortality due to lung cancer. CONCLUSIONS--The results suggest that episodic symptoms, which often do not appear in standard respiratory questionnaires, predict subsequent mortality from chronic obstructive airways disease. This supports the hypothesis that reversible airflow obstruction may be a precursor of progressive and irreversible decline in ventilatory function.     

INTERMITTENT POSITIVE PRESSURE BREATHING—A Clinical Evaluation of Its Use in Certain Respiratory Diseases

A series of patients with chronic respiratory insufficiency were treated with intermittent positive pressure breathing, which was combined with administration of bronchodilator drugs of the epinephrine series. Spirographs were made before and after treatment. The series included patients with chronic bronchitis and emphysema, fibrosis of various kinds, senile emphysema and bronchogenic carcinoma.Although the majority showed objective improvement, a significant proportion in all groups did not, and some were made worse, apparently on a basis of check valve mechanisms unresolved by the bronchodilator drug. In cases in which the method benefited the patient, the benefit was greater than that obtained with bronchodilator drugs alone.     

Intermittent positive pressure breathing: a clinical evaluation of its use in certain respiratory diseases

A series of patients with chronic respiratory insufficiency were treated with intermittent positive pressure breathing, which was combined with administration of bronchodilator drugs of the epinephrine series. Spirographs were made before and after treatment. The series included patients with chronic bronchitis and emphysema, fibrosis of various kinds, senile emphysema and bronchogenic carcinoma. Although the majority showed objective improvement, a significant proportion in all groups did not, and some were made worse, apparently on a basis of check valve mechanisms unresolved by the bronchodilator drug. In cases in which the method benefited the patient, the benefit was greater than that obtained with bronchodilator drugs alone.     

Regional Lung Function in Patients with Obstructive Lung Diseases

Regional lung function was measured, using radioactive xenon-133, in a group of normal subjects and in three carefully defined groups of patients with obstructive lung disease. When compared with the normal subjects, patients in the emphysematous group showed a relative reduction of ventilation and perfusion to the upper zones, while patients having chronic bronchitis without cardiac or respiratory failure showed a predominantly lower zone defect. In the group of patients with chronic bronchitis with cardiac and respiratory failure no consistent pattern was found.     

Comparison of physiotherapy,manipulation, and corticosteroid injection for treating shoulder complaints in general practice: randomised,single blind study.

OBJECTIVE: To compare the efficacy of physiotherapy, manipulation, and corticosteroid injection for treating patients with shoulder complaints in general practice. DESIGN: Randomised, single blind study. SETTING: Seven general practices in the Netherlands. SUBJECTS: 198 patients with shoulder complaints, of whom 172 were divided, on the basis of physical examination, into two diagnostic groups: a shoulder girdle group (n = 58) and a synovial group (n = 114). INTERVENTIONS: Patients in the shoulder girdle group were randomised to manipulation or physiotherapy, and patients in the synovial group were randomised to corticosteroid injection, manipulation, or physiotherapy. MAIN OUTCOME MEASURES: Duration of shoulder complaints analysed by survival analysis. RESULTS: In the shoulder girdle group duration of complaints was significantly shorter after manipulation compared with physiotherapy (P < 0.001). Also the number of patients reporting treatment failure was less with manipulation. In the synovial group duration of complaints was shortest after corticosteroid injection compared with manipulation and physiotherapy (P < 0.001). Drop out due to treatment failure was low in the injection group (17%) and high in the manipulation group (59%) and physiotherapy group (51%). CONCLUSIONS: For treating shoulder girdle disorders, manipulation seems to be the preferred treatment. For the synovial disorders, corticosteroid injection seems the best treatment.     

Prevalence and diagnosis of chronic respiratory symptoms in adults.

OBJECTIVE--To investigate the prevalence and diagnosis of chronic respiratory disease in adults. DESIGN--Screening questionnaire was sent to all patients aged 40-70 on the register of a group general practice; those responding positively were sent a detailed questionnaire and invited for assessment of respiratory function by forced expiratory volume in one second, forced vital capacity, peak flow rate, and reversibility studies with a beta adrenergic inhaler. SETTING--Group general practice in south west London. RESULTS--Of 2387 patients aged 40-70, 1444 completed a screening questionnaire. Of the 509 patients who reported cough, phlegm, wheeze, or shortness of breath, 324 responded to a detailed questionnaire, 256 of whom had simple respiratory function assessed. Chronic bronchitis affected 106 (17%) men and 58 (7%) women, and wheeze occurring at least once a week affected 60 (9%) men and 20 (3%) women. Only a half to a third of patients had received a diagnostic label of chronic bronchitis or asthma for their symptoms. There was considerable clinical and physiological similarity (including reversibility of the airways) between patients labelled as having asthma and having chronic bronchitis. A label of asthma was used more often for patients of social classes I and II. CONCLUSIONS--Comparison with prevalence surveys carried out in the 1950s showed that respiratory symptoms are as common now as then, but the risk of disabling chronic bronchitis has fallen, more among men than women, probably because of their reduced smoking. Changes in diagnostic fashion, together with increased detection, may have contributed to the upward trend in reported morbidity from asthma over the past 30 years.     

Use of Benzoctamine as Sedative in Patients with Respiratory Failure

Benzoctamine (Tacitin) was given by mouth as night sedation to patients admitted to hospital with respiratory failure. Fourteen patients had chronic obstructive bronchitis and six had acute severe asthma. One patient with asthma needed intravenous sedation with benzoctamine. No adverse effects were observed, and there was no significant change of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), or Pco₂ in any patient after benzoctamine. Nevertheless, further clinical experience of the drug is required before its use can be safely recommended in respiratory failure.     

Evaluation of the forced expiration technique as an adjunct to postural drainage in treatment of cystic fibrosis.

Sixteen patients with cystic fibrosis were treated with conventional physiotherapy aided by an assistant. The results were compared with those produced by physiotherapy using the forced expiration technique cleared more sputum in less time than conventional physiotherapy. A sputum in less time than conventional physiotherapy. A second study showed that an assistant did not further improve the results obtained by the patient performing the forced expiration technique himself. These findings mean that patients with cystic fibrosis who have had to rely on the help of others for their home treatment may now perform more effective treatment without help. The forced expiration technique might also be helpful for patients with chronic bronchitis, asthma, or bronchiectasis.     

Chronic hypobaric hypoxia increases isolated rat fast-twitch and slow-twitch limb muscle force and fatigue

Chronic hypoxia alters respiratory muscle force and fatigue, effects that could be attributed to hypoxia and/or increased activation due to hyperventilation. We hypothesized that chronic hypoxia is associated with phenotypic change in non-respiratory muscles and therefore we tested the hypothesis that chronic hypobaric hypoxia increases limb muscle force and fatigue. Adult male Wistar rats were exposed to normoxia or hypobaric hypoxia (PB=450 mm Hg) for 6 weeks. At the end of the treatment period, soleus (SOL) and extensor digitorum longus (EDL) muscles were removed under pentobarbitone anaesthesia and strips were mounted for isometric force determination in Krebs solution in standard water-jacketed organ baths at 25 °C. Isometric twitch and tetanic force, contractile kinetics, force-frequency relationship and fatigue characteristics were determined in response to electrical field stimulation. Chronic hypoxia increased specific force in SOL and EDL compared to age-matched normoxic controls. Furthermore, chronic hypoxia decreased endurance in both limb muscles. We conclude that hypoxia elicits functional plasticity in limb muscles perhaps due to oxidative stress. Our results may have implications for respiratory disorders that are characterized by prolonged hypoxia such as chronic obstructive pulmonary disease (COPD).     

Criteria of fitness for anaesthesia in patients with chronic obstructive lung disease.

Twelve patients with severe chronic obstructive lung disease undergoing 15 operations were assessed with preoperative lung function tests and blood gas estimations. Their operative and postoperative course was followed. There were no deaths or serious complications. Patients fell into three groups: those with low respiratory capacity but normal blood gases, who required no special respiratory treatment apart from physiotherapy and antibiotics; those with hypoxaemia but normal arterial carbon dioxide pressure, who needed more prolonged oxygen treatment after operation; and those with hypoxaemia and hypercapnia, who needed postoperative ventilatory support. While forced expiratory volume in one second (FEV) is a good screening test in preoperative assessment it should be supplemented by arterial blood gas estimations in patients with an FEV of less than 1 litre.     

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O₂ saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O₂-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.     

Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis

Background

The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function. The aims of this study were to investigate total mortality risks in GOLD stages 0–4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1–4.

Method

Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits. Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses. Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0–4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group. HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1–4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.

Results

The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively. The proportion of smokers among men was 50% and among women 40%. Self reported comorbidity was present in 4.6% of the men and 6.6% of the women. Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32–2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31–1.70). The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98–1.29). Among male smokers with stage 1; HR: 2.04 (1.34–3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38–7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.

Conclusion

Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2).     

Role of polymorphic variants of cytochrome P450 genes (CYP1A1, CYP2E1) and microsomal epoxide hydrolase (mEPHX) in pathogenesis of cystic fibrosis and chronic respiratory tract diseases

Frequencies of CYP1A1, CYP2E1, and mEPHX polymorphic variants were analyzed in cystic fibrosis, chronic obstructive lung disease, bronchiectatic disease, chronic nonobstructive bronchitis, and recurring bronchitis. Mutations in CYP1A1 and mEPHX were shown to modify the severity of respiratory disorders in cystic fibrosis, the combination of CYP1A1 genotype Val/Val with the "very slow" mEPHX phenotype being most unfavorable (odds ratio OR = 12.30). Heterozygosity at both CYP1A1 and CYP2E1 was associated with chronic obstructive lung disease and recurring bronchitis (OR = 4.08 and 11.72, respectively). The "very slow" phenotype of mEPHX was predisposing to chronic respiratory disorders regardless of the CYP1A1 or CYP2E1 alleles (OR = 4.06). Basing on the above correlations, a combination of the "very slow" mEPHX phenotype with elevated cytochrome P450 (CYP1A1 and CYP2E1) activities was assumed to expedite severe respiratory disorders.     

Relation between lung cancer,chronic bronchitis,and airways obstruction.

Since cigarette smoking is an important cause of lung cancer and chronic bronchitis both conditions should occur together more often in cigarette smokers than would result from chance. If they do commonly occur together then severe airways obstruction, which is often associated with chronic bronchitis, should also be often associated with lung cancer. To discover whether this were so three groups of patients were studied at the London Chest Hospital. Two hundred men and 43 women who presented with lung cancer provided information on the prevalence of defined chronic bronchitis and airways obstruction in those suffering from lung cancer. The third group consisted of 233 men presenting with defined chronic bronchitis who were kept under observation to discover how many would die from lung cancer. The results suggested that simple bronchitis and lung cancer often occur together but that obstructive bronchitis and lung cancer do not often occur together. The lack of association between lung cancer and severe airways obstruction requires an explanation.     

痰热清注射液对老年慢性支气管炎急性发作的疗效和免疫功能的影响

目的:探讨痰热清注射液治疗老年慢性支气管炎急性发作的临床疗效,观察患者治疗前后细胞因子的变化。方法:选择我院2011年1月至2012年6月收治的老年慢性支气管炎急性发作的患者80例,随机分为研究组和对照组,各40例。两组均给予常规吸氧、解痉、平喘化痰等药物治疗,同时给予头孢呋辛静脉滴注,2次/d;研究组同时给予痰热清注射液静脉滴注,1次/d,7d为一个疗程,共2个疗程。治疗前后应用酶联免疫吸附法测量两组血清肿瘤坏死因子a(Tumor necrosis factor-a,TNF-a)、白介素-6(Interleukin-6,IL-6)、IL-8水平。结果:1研究组患者咳嗽改善时间、呼吸困难改善时间和肺部湿啰音改善时间明显短于对照组(P0.05)。研究组总有效率明显高于对照组(P0.05)。2治疗后两组血清IL-6、IL-8、TNF-a水平明显降低(P0.05);研究组血清IL-6、IL-8、TNF-a水平明显低于对照组(P0.05)。结论:痰热清治疗老年慢性支气管炎急性发作可以有效改善患者临床症状,调节免疫功能,降低炎症反应,治疗效果较好。     

慢性支气管炎患者下呼吸道感染病原菌分布及耐药性分析

目的:研究老年慢性支气管炎患者合并下呼吸道感染病原菌分布以及耐药性。方法:选取2009年1月到2013年12月我院收治的老年慢性支气管炎患者合并下呼吸道感染患者261例,采集所有患者的痰液,然后进行病原菌鉴定和药敏试验。结果:261例患者中,144例革兰阴性杆菌感染(55.2%),51例革兰阳性杆菌感染(19.5%),66例真菌感染(25.3%),其中混合感染者36例(13.8%)。革兰阴性杆菌以肺炎克雷伯菌最多(18.4%),革兰阳性杆菌以金黄色葡萄球菌最多(9.2%)。革兰阴性杆菌对亚胺培南的耐药性最低,其次是头孢哌酮和阿米卡星,对氨苄西林耐药率最高。金黄色葡萄球菌和表皮葡萄球菌对青霉素的耐药率均为100.0%,均对万古霉素敏感,其次是对环丙沙星敏感。结论:老年慢性支气管炎患者合并下呼吸道感染以革兰阴性杆菌感染为主,真菌和混合感染也占一定的比例,应该引起注意。     

痰热清注射液联合纳洛酮对老年慢性呼吸衰竭并发肺性脑病患者临床疗效的影响

目的:探讨痰热清注射液联合纳洛酮对老年慢性呼吸衰竭并发肺性脑病患者临床疗效的影响。方法:选取我院呼吸科收治的慢性呼吸衰竭并发肺性脑病患者60例,随机分为治疗组和对照组,每组30例。对照组给予加痰热清注射液治疗,治疗组在对照组治疗基础上联合纳洛酮注射液治疗。治疗结束后,比较治疗前后两组患者动脉血气分析结果、血清BNP(脑钠肽)、SOD(超氧化物歧化酶)、MDA(丙二醛)水平及临床疗效。结果:与治疗前相比,两组患者治疗后的血清BNP、MDA水平降低,SOD水平升高(P0.05),PaO_2水平升高,PaCO_2水平下降(P0.05);与对照组比较,治疗组总有效率较高,BNP、MDA水平较低,SOD水平较高(P0.05),PaO_2水平较高,PaCO_2水平较低(P0.05)。结论:痰热清注射液联合纳洛酮治疗老年慢性呼吸衰竭并发肺性脑病临床疗效好,推测其机制与降低血清BNP、MDA及升高血清SOD水平有关。     

EPs® 7630-solution – an effective therapeutic option in acute and exacerbating bronchitis

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs^® 7630 (Umckaloabo^®), which has been tested against placebo in double-blind clinical trials. EPs^® 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs^® 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1±2.8 points on average at the start of treatment and decreased by 3.3±3.8 points to 2.8±2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.     

Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by (31)P-NMR spectroscopy.

Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured P(i) and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 +/- 7 to 61 +/- 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 +/- 17 to 19 +/- 11 mmHg) and evidence of metabolic stress (ratio of P(i) to PCr increased by 290%; from 0.19 +/- 0.09 to 0.74 +/- 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure.