Monoclonal antibodies for asthma and chronic obstructive pulmonary disease

Introduction: In asthma and chronic obstructive pulmonary disease (COPD), the inflammation in the airways cannot always be controlled with conventional therapies, such as inhaled corticosteroids. Addition of more specific anti-inflammatory therapies, such as monoclonal antibodies, against inflammation pathways might improve the disease outcome.

Areas covered: This review individually discusses the major inflammation pathways and their potential blocking monoclonal antibodies in asthma and COPD.

Expert opinion: The current use of omalizumab in asthma provides a good example on the potential therapeutic role of monoclonal antibodies in both asthma and COPD. There are many other monoclonal antibodies which are currently investigated as possible therapies in these diseases. The identification of the disease subsets in which such antibodies might exert the maximum benefit opens the door for personalized medicine and for targeted biological therapy in asthma and COPD.     

Distinguishing chronic obstructive pulmonary disease from asthma

Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic respiratory diseases in the UK. Good management of both diseases results in better symptom control and improved quality of life for the patient, but will rely on all members of the primary healthcare team sharing the aims of management as well as helping to implement those goals. The two diseases share many clinical features and similar drugs can be used to treat them both. However there are important clinical differences which help to distinguish them from each other. The management of the two diseases differs in drug regimens and in the long-term aims of management. This article clarifies the important features that distinguish asthma from COPD and which allow patients to receive the best specific management.     

Targeting the NF-kappaB pathway in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide. While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases. Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance. Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers. There are now excellent reasons to promote NF-kappaB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease. This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-kappaB mediated signalling events in several cell types. Also, a range of inhibitors of NF-kappaB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-kappaB decoy sequences, small molecule inhibitors such as IKK-beta inhibitors, and proteasome inhibitors affecting NF-kappaB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders. This review will focus on the role of NF-kappaB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-kappaB as a therapeutic target in these two important inflammatory lung diseases.     

The cytokine network in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases.     

慢性阻塞性肺疾病和支气管哮喘生理评分在疾病急性加重期护理中的应用价值

目的 探讨慢性阻塞性肺疾病和支气管哮喘生理评分(the COPD and Asthma Physiology Score,CAPS)能否正确评估慢性阻塞性肺疾病急性加重期(AECOPD)患者病情的严重性和预后,指导治疗和护理计划的制定.方法 对我科2008年9月～2010年5月住院的AECOPD患者进行回顾性分析和CA...     

Measurement of fatigue in chronic obstructive pulmonary disease and in asthma

Despite recognition of a high prevalence of fatigue in individuals with chronic airflow obstruction conditions, including chronic obstructive pulmonary disease and asthma, and its importance from a quality of life perspective, no research was found in which fatigue was measured directly in these populations. This may be due to a seeming lack of appropriate instruments for measuring fatigue in these populations. The purpose of this study, therefore, was to pretest an instrument, the Piper Fatigue Scale, which was developed to measure chronic fatigue in clinical populations. The outpatient sample consisted of 17 persons with chronic obstructive pulmonary disease and 19 with asthma. Findings revealed that the visual analogue scale version of the Piper Fatigue Scale may not be appropriate for measuring fatigue in these populations. Instruments with validity and reliability for fatigue in chronic obstructive pulmonary disease and asthma need to be developed.     

Epidemiology of chronic obstructive pulmonary disease in Japan--international comparison

Substantial variation among countries has been reported regarding mortality data for COPD in industrialized countries. Differences in COPD death rates among countries have attracted considerable attention, with multiple suggested hypothesis, including smoking behaviors, air pollution, respiratory infections and genetic factors. However, the lack of standardization of death certification as well as differences among countries in diagnostic standards of COPD, could limit the interpretation of the data. No meaningful international comparisons of COPD prevalence can be possible until a GOLD initiative bring information about COPD to public health officials, the medical community, and the public throughout the world. No comparable data regarding the COPD epidemiology such as Nippon COPD Epidemiology(NICE) study, has been available in other countries than Japan. NICE study indicated that most of COPD cases(90%) are undiagnosed, and a significant attention will be required to raise awareness of COPD.     

Ventilation of patients with asthma and chronic obstructive pulmonary disease

Ventilatory intervention is often life-saving when patients with asthma or chronic obstructive pulmonary disease (COPD) experience acute respiratory compromise. Although both noninvasive and invasive ventilation methods may be viable initial choices, which is better depends upon the severity of illness, the rapidity of response, coexisting disease, and capacity of the medical environment. In addition, noninvasive ventilation often relieves dyspnea and hypoxemia in patients with stable severe COPD. On the basis of current evidence, the general principles of ventilatory management common to patients with acutely exacerbated asthma/COPD are these: noninvasive ventilation is suitable for a relatively simple condition, but invasive ventilation is usually required in patients with more complex or more severe disease. It is crucial to provide controlled hypoventilation, longer expiratory time, and titrated extrinsic positive end-expiratory pressure to avoid dynamic hyperinflation and its attendant consequences. Controlled sedation helps achieve synchrony of triggering, power, and breath timing between patient and ventilator. When feasible, noninvasive ventilation often facilitates the weaning of ventilator-dependent patients with COPD and shortens the patient's stay in the intensive care unit.     

Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory disorders of the respiratory tract that are characterized by airflow limitation. They are distinct conditions with different causes, structural changes, and immunopathology. The pathophysiology in asthma and COPD involves not only the proximal large airways, but also the distal small airways, and thus the small airways are an important therapeutic target in the treatment of both diseases. The assessment of diseased distal small airways is challenging. Extensive disease can be present in the small airways with little abnormality in conventional pulmonary function tests. Recent advances in imaging technologies have led to better spatial resolution to assess small airways morphology non-invasively. New physiological tests have been developed to detect disease and response to therapy in regional airways. Improving the efficiency of existing aerosolized therapy to direct drug to the appropriate lung regions may improve clinical efficacy. Approaches to target distal lung regions include developing new drug formulations with smaller aerosol particle size or using inhaler devices that emit aerosolized drug at slow inhalation flows. Large studies are needed to determine whether better distal lung deposition leads to improvements in small airways function that are translated into clinically significant patient outcomes.     

The myocardial condition in chronic obstructive pulmonary disease and bronchial asthma

The purpose of the study was to assess the influence of structural and functional changes in the myocardium of the right and left ventricle (RVand LV) on the development of ischemia and arrhythmia in chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA). The subjects of the study were 156 patients with either persistent BA (81 patients) or COPD (75 patients). Patients with decompensated cor pulmonale were excluded. ECG, 24-hour ECG monitoring, and echocardioscopy were performed. The study found that the occurrence of supraventricular and ventricular extrasystoles (SVES and VES) in patients with mild COPD or BA depended on the condition of RV diastolic function and on LV diastolic function and myocardial ischemia as well in COPD. In moderate BA the processes of myocardial remodeling correlate with myocardial ischemia, RV dysfunction and increased pulmonary arterial pressure (PAP), as well as with lipid dismetabolism. The appearance of SVES in patients with severe BA is connected with interventricular septal hypertrophy, LV dysfunction, and increased PAP, while VEC appear due to myocardial ischemia and hypercholesterolemia. In severe COPD the occurrence of SVES and VES does not depend on structural and functional changes in the myocardium, while myocardial ischemia is connected with LV hypertrophy. In BA ischemia depends on the development of RV and LV diastolic dysfunction, as well as hypercholesterolemia.     

Double-blind comparison of tulobuterol and salbutamol in chronic obstructive pulmonary disease

A double-blind study compared tulobuterol (2 mg BID), a new beta 2-adrenergic agent, with salbutamol (2 mg TID) in 40 hospitalized men with chronic obstructive pulmonary disease. The study evaluated the bronchospasmolytic effects of the two drugs and their selectivity of action. Measurements and observations were made for six hours after the first oral dose, daily during nine days of continuous therapy, and for 12 hours after the final dose on the tenth day. Results show that the tulobuterol regimen produced a significant (P less than 0.01) improvement of the forced expiratory volume in one second equal to an increase of 25% above the pretreatment value, versus 16% with the salbutamol regimen. Cardiovascular effects appeared more rapidly with tulobuterol, but they stabilized to values lower than those observed with salbutamol. No clinically important adverse reactions were reported other than slight tremor, which was not objectionable.     

A comparison of twice- versus once-weekly supervision during pulmonary rehabilitation in chronic obstructive pulmonary disease

OBJECTIVE: To compare the effects of twice- versus once-weekly supervised pulmonary rehabilitation on exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, randomized, parallel-group study. SETTING: Hospital outpatient physiotherapy department. PARTICIPANTS: Patients with COPD. INTERVENTION: Group 1 (n=46) received 1 supervised exercise session a week and 2 unsupervised sessions; group 2 (n= 45) received 2 supervised exercise sessions a week and 1 unsupervised session for 6 weeks. Patients were assessed at baseline and at 6 weeks, 2 months, and 6 months. MAIN OUTCOME MEASURES: Incremental (ISWT) and endurance (ESWT) shuttle walk tests and Chronic Respiratory Disease Questionnaire (CRDQ). RESULTS: Sixty-six of 91 patients (group 1, n=34; group 2, n=32) completed the 6-week program. There was no significant difference in key outcome measures between the 2 groups (ISWT, 13.50m; 95% confidence interval [CI], -10.06 to 37.15m; ESWT, 72.64s; 95% CI, -96.01 to 241.29s; CRDQ total score, 2.54; 95% CI, -3.16 to 8.24). The results of the ESWTs suggest there may be an interaction between baseline exercise capacity and benefit of pulmonary rehabilitation, with more disabled patients achieving greater benefit if they are supervised twice weekly. Irrespective of group, allocation benefits after pulmonary rehabilitation had almost dissipated by 6 months. CONCLUSIONS: There was no difference in the effectiveness of twice- versus once-weekly supervised pulmonary rehabilitation. This study highlights the need for development of strategies that will maintain the improvement achieved by the initial pulmonary rehabilitation program.