Respiratory Disease Research Research Articles

Beyond a shadow of a doubt? Experts, lay knowledge, and the role of radiography in the diagnosis of silicosis in Britain, c. 1919-1945.

The history of silicosis provides an important chapter in the history of occupational and environmental health. Recent historical scholarship has drawn attention to the importance of patient attitudes, popular protests, and compensation claims in the formation of a "lay epidemiology" of such a disease, frequently challenging the scientific orthodoxies devised by large corporations and medical specialists. Surprisingly little research has been undertaken on the United Kingdom, which provided much of the early expertise and medical research in respiratory diseases among industrial workers. This article examines the introduction of a particular technique, x-radiography, and its use by radiologists and others in debates on the causes and consequences of silica inhalation by the laboring population in Britain during the early decades of the twentieth century. In contrast to some recent interpretations, and also to the narrative of progress that practitioner historians have developed since the 1940s, this article suggests that the use of this technology was contested for much of this period and the interpretation of X-rays remained disputed and uncertain into the 1950s. The article also questions recent accounts of lay epidemiology as an adequate model for understanding the progress of such innovations in medical history.

High ethionamide resistance in Mycobacterium tuberculosis strains isolated in Kenya

SUMMARY Background: Increasing development of tuberculosis (TB) resistance to the currently available drugs including second-line anti-TB drugs that are being used for treatment of Multi-Drug Resistant TB (MDR-TB) patients has frustrated efforts to control TB worldwide. Ethionamide (Eth) is one of the drugs used in the regimen for treatment of these patients. Objective: To determine level of Ethionamide resistance among second-line anti-tuberculosis drugs in Mycobacterium tuberculosis (MTB) strains isolated in Kenya. Design: A retrospective lab-based study involving archived strains from previous studies carried out at the Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI) from 2002 to 2007. Setting: Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI). Methods: A total of 216 MTB strains with pre-determined first-line drug susceptibility testing (DST) results were used including 78 first-line resistant to individual and combined drugs, and 138 susceptible to streptomycin, rifampicin, isoniazid and ethambutol. The strains were subjected to DST to ethionamide among other second-line. Results: Thirty two [32/216 (14.8%)] strains showed resistance to second-line drugs. Resistance to Eth was the highest [18/32 (56.3%)] including co-resistance with isoniazid [8/18 (44.4%)]. Nine [9/18 (50%)] strains were fully resistant and 9 [9/18 (50%)] were intermediate resistant to Eth. Conclusion: Unexplainable high levels of Eth resistance is a cause for concern. This will impact negatively on the outcome of management of MDR-TB especially in Kenya where the use of this drug is almost mandatory. Close monitoring of Eth before initiating individual patient management may be necessary.

Bovine respiratory disease research (1983–2009)

Bovine respiratory disease (BRD) research has provided significant understanding of the disease over the past 26 years. Modern research tools that have been used include monoclonal antibodies, genomics, polymerase chain reaction, immunohistochemistry (IHC), DNA vaccines and viral vectors coding for immunogens. Emerging/reemerging viruses and new antigenic strains of viruses and bacteria have been identified. Methods of detection and the role for cattle persistently infected bovine viral diarrhea virus (BVDV) were identified; viral subunits, cellular components and bacterial products have been characterized. Product advances have included vaccines for bovine respiratory syncytial virus, Mannheimia haemolytica and Pasteurella multocida; the addition of BVDV2 to the existing vaccines and new antibiotics. The role of Mycoplasma spp., particularly Mycoplasma bovis in BRD, has been more extensively studied. Bovine immunology research has provided more specific information on immune responses, T cell subsets and cytokines. The molecular and genetic basis for viral-bacterial synergy in BRD has been described. Attempts have been made to document how prevention of BRD by proper vaccination and management prior to exposure to infectious agents can minimize disease and serve as economic incentives for certified health programs.

Future of BRD research: an animal health industry perspective

Industry has made large investments into bovine respiratory disease (BRD) research historically, and will continue to do so, despite the apparent lack of progress, an uncertain regulatory environment, and increased competition for internal resources. Factors such as the growing demand for protein, and the ongoing consolidation and 'technification' of the beef sector globally suggest that the industry will continue to demand interventions that prevent disease, are more efficacious, can be easily administered, and positively affect meat quality. New products must also meet the regulatory requirements of safety and efficacy and anticipate the future needs of the numerous stakeholders in the global food chain. Two obstacles in meeting this challenge are the declining interest in food animal medicine, and BRD specifically, and the reluctance to accept new technology at the consumer level.

NHLBI Workshop: Respiratory Medicine-Related Research Training for Adult and Pediatric Fellows

The pulmonary physician-scientist has a special niche to generate basic research findings and apply them to a clinical disease and perhaps impact its medical care. The availability of new high throughput-based scientific technologies in the "omics era" has made this an opportune time for physician scientists to prepare and embark on an academic career in respiratory disease research. However, maintaining an adequate flow through the research pipeline of physician-scientist investigators studying respiratory system diseases is currently a challenge. There may not be a sufficient workforce emerging to capitalize on current research opportunities. The National Heart, Lung, and Blood Institute (NHLBI) organized a workshop to assess ways to attract and properly train advanced fellows to pursue research careers in adult and pediatric lung diseases. Participants included representatives from the various pulmonary training programs, respiratory-related professional societies, and NHLBI staff. Deliberation centered on present barriers that might affect interest in pursuing research training, devising better incentives to attract more trainees, and how current research support offered by the NHLBI and the Professional Societies (in partnership with Industry and Patient Support groups) might be better coordinated and optimized to ensure a continued pipeline of pulmonary investigators. Major recommendations offered are: (1) Attract trainees to pulmonary/critical care medicine-based research careers by increasing research exposure and opportunities for high school, college, and medical students. (2) Increase awareness of the outstanding physician-scientist role models in the lung community for trainees. (3) Facilitate mechanisms by which the lung community (NHLBI, professional societies, and partners) can better support and bridge senior fellows as they transition from Institutional Training Grants (T32) to Career Series (K) awards in their early faculty career development.

Strategic Plan for Pediatric Respiratory Diseases Research: An NHLBI Working Group Report

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease; sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases; (2) injury, regeneration, and repair in the developing lung; (3) pulmonary vascular disease in children; (4) development and adaptation of ventilatory responses to postnatal life; (5) nonatopic wheezing: aberrant large airway development or injury?; (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases; and (7) predictive and personalized medicine for children.

Strategic plan for pediatric respiratory diseases research: An NHLBI working group report

The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalized medicine for children.

The Pipeline: Preparing and Training Pulmonary Scientists for Research Careers

New technologies have made this an opportune time to prepare and embark on an academic career in respiratory disease research. The pulmonary physician-scientist has a special advantage to take basic research findings to the patient's illness and impact medical care. But is there a sufficient work force emerging to capitalize on current research opportunities? The aim of this study was to analyze the present workforce of potential clinical investigators available by reviewing the mechanisms of training support as provided by the National Heart Lung and Blood Institute (NHLBI) and by the professional pulmonary societies, including their patient advocacy groups and pharmaceutical partners, and by discussing how support for research training might be improved for advanced clinical fellows. Of the approximately 500 fellows/year in a final training year in Pulmonary/Critical Care Medicine and related programs, about one third are involved mainly in supervised research and of whom about two thirds plan to continue fellowship training for an additional year or more (approximately 100-120 trainees). It seems especially important to encourage his particular group who are planning to extend fellowship for research training. Both the NHLBI and the professional pulmonary societies and their partners provide support for advanced fellowship trainees, but resources are limited. To insure that enough well-trained new clinical investigators will be available to conduct future pulmonary research, funding support and other career inducements should be discussed collectively by the NHLBI and the professional pulmonary societies for the purpose of optimizing support for advanced fellowship trainees.

Cannabis and lung cancer

To the Editors: The elegant and eminent study by Aldington et al. 1 of the Cannabis and Respiratory Disease Research group is to be welcomed at a time when, as the authors rightly point out, there are many suggestive case studies and clinical series on lung cancer, and indeed other tumours, occurring particularly at younger ages in past and present smokers of cannabis. The authors' careful methodology and succinct summary of much of the relevant literature in relation to this subject is a relevant and timely addition to the literature, particularly in the context of increased interest in this subject in both lay and professional circles. The point made by Aldington et al. 1 in relation to the lack of research into the molecular underpinnings of cannabis-related oncogenesis is particularly relevant at a period in research history when the molecular bases of disease have received unprecedented attention. It …

Improved diagnosis of Ziehl-Neelsen smear negative tuberculosis using sodium hypochlorite sedementation method

Bacteriological diagnosis of tuberculosis (TB) is largely dependent on Ziehl-Neelsen (ZN) microscopy. This method has a low sensitivity. Although concentration of sputum with sodium hypochlorite (NaOC1) followed by sedimentation increases the sensitivity of direct smear microscopy, no study has focused on the effect of NaOC1 on smear negative sputum specimens. To establish whether 3.5% NaOC1 sedimentation method specifically improves the diagnosis of Ziehl-Neelsen smear negative tuberculosis. A prospective study. Mbagathi District Hospital and Center for Respiratory Diseases Research, Kenya Medical Research Institute. Two hundred and thirty confirmed direct ZN smear negative sputum specimens from new TB suspects were analysed. Seventy (30.4%) specimens were culture positive. Of these, 19 were ZN smear positive. The ZN sensitivity, specificity, positive and negative predictive values were 27.1%, 99%, 95% and 76%, respectively, after sedimentation with 3.5% NaOC1. Overnight sedimentation using 3.5% NaOC1 significantly improves diagnosis of ZN smear negative TB. This technique has potential to improve diagnosis in TB diagnostic services especially in settings with high burden of dual TB/HIV infection.

Combination of bleach and flourescent microscopy: a milestone in the diagnosis of smear negative tuberculosis

The reliability of direct smear microscopy for diagnosis of tuberculosis has frequently been questioned due to low sensitivity. Treatment of sputum with sodium hypochlorite (NaOCI) has been used to increase sensitivity in many settings. However, no study has established the effect of NaOCI on fluorescent microscopy. To establish whether NaOCI concentration method enhances positivity of fluorescent microscopy smear negative sputum for diagnosis of tuberculosis. A prospective study. Mbagathi District Hospital and Centre for Respiratory Diseases Research, Kenya Medical Research Institute. Forty five (22%) specimens were culture positive. Fluorescent microscopy sensitivity was 28.9% and 22.2% after centrifugation and sedimentation with 3.5% NaOCI, respectively (P > 0.05). Sensitivity was 24.4% and 17.8% after centrifugation and sedimentation with 5% NaOCI, respectively (P > 0.05). Although there was no statistical significance difference between the two NaOCI concentration methods, 3.5% NaOCI with centrifugation indicated a higher yield. Use of NaOCI significantly enhances positivity of smear negative sputum for diagnosis of tuberculosis when used with fluorescent microscopy. This approach could be recommended for screening all tuberculosis suspects especially in settings with potential smear negative tuberculosis.

A Holy Grail of asthma management: toward understanding how long‐acting β2‐adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS) -- i.e. glucocorticoid -- and an inhaled long-acting beta(2)-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449-456; N Engl J Med 2007, 356: 775-789) reporting for the 'TRial of Inhaled STeroids ANd long-acting beta(2)-agonists (TRISTAN)' and 'TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new 'optimized' LABA/ICS combination therapies.

Emerging infections: what have we learned from SARS?

Emerging infections: what have we learned from SARS?

International Trends of Outcomes Research in Respiratory Diseases

International Trends of Outcomes Research in Respiratory Diseases

NHLBI: fifty years of achievement in pulmonary biology and medicine.

On June 16, 1948, the National Heart Act (P.L. 80-655) authorized the formation of the National Heart Institute (NHI) to “improve the health of the people of the United States through the conduct of researches, investigations, experiments, and demonstrations relating to the cause, prevention, and method of diagnosis and treatment of diseases of the heart and circulation; assist and foster such researches and other activities by public and private agencies, and promote the coordination of all such researches and activities and the useful application of their results; provide training in matters related to heart diseases, including refresher courses for physicians; and develop, and assist states and other agencies in use of the most effective methods of prevention, diagnosis and treatment of heart diseases.” Although the NHI focused its efforts mainly on heart disease, its programs from the beginning included many projects on cardiopulmonary physiology. Research on topics such as fluid balance, muscle biology, control of breathing, high-altitude physiology, and hyperbaric medicine were part of the grant portfolio. These investigations paved the way for formal recognition of a long-standing need for a national program committed to diseases of the lung when the Secretary of the Department of Health, Education, and Welfare announced in November 1969 an expansion of the NHI to the National Heart and Lung Institute (NHLI). * At that time, the National Institutes of Health (NIH) was providing $11.0 million for support of research and training in respiratory diseases, but these activities were dispersed among various institutes, with little integration and no mechanism for coordination. Shortly after issuance of the new charter, several administrative actions were taken: ( 1 ) the NIH Guidelines for Referral were modified to reflect the expanded role of the NHLI; ( 2 ) the National Heart and Lung Advisory Council was increased from 12 to 16 members (Table 1); ( 3 ) an Office of Lung Programs was established in the NHLI; and ( 4 ) an intramural pulmonary program was initiated with establishment of a Pulmonary Function Laboratory in March 1971 and, shortly thereafter, a Pulmonary Branch for Intramural Research. In September 1972 Congress enlarged the authority of the Institute through the National Heart, Blood Vessel, Lung, and Blood Act (P.L. 92-423), which provided for expanded, intensified, and coordinated Institute activities in lung disease research and training. This action launched the formation of the Division of Lung Diseases and the beginning of intense research efforts in all aspects of pulmonary biology and medicine (with the exception of lung cancer, which remained in the National Cancer Institute, and infectious lung diseases, which remained the responsibility of the National Institute of Allergy and Infectious Diseases). In this report, we highlight some of the administrative steps that were taken and acknowledge the contributions of some individuals and groups that played an important role in guiding the implementation and evaluation of the national pulmonary research effort. As we mark the 50th anniversary of the NHLBI, it is clear that throughout the history of the Institute, a close and valuable collaboration in cardiopulmonary medicine must be recognized as contributing to a vast knowledge base that served as the foundation for many important discoveries made in this last half-century.

Possibilities for future cooperation within the field of respiratory physiology and pharmacology.

From the viewpoint of clinical research in respiratory diseases the situation seems promising. On one hand, there are a lot of unanswered questions in pulmonology. And on the other, there are possibilities to solve these questions, by the combination of research experience, facilities, patients, and last but not least--individual initiatives. Shortage of money has the positive effect in maintaining the simple and reliable old skills in research and clinical practice as there are few sophisticated and expensive apparatus to rely on. The physicians must also be very inventive to help their patients when medical supplies are insufficient. Therefore, success in science and in scientific cooperation is determined by the persons engaged. Finding capable and dedicated people is crucial and the most vital challenge to whatever project. And such people can be found on both sides of the Baltic Sea. In conclusion, this short description of differences between the Baltic States and the Nordic countries could, give some clues for future cooperation. Based on the well known key-lock model of pharmacology, team-work between different talents will give results not attainable individually. When all think alike, nobody thinks.

Respiratory mechanics in normal bonnet and rhesus monkeys

We measured lung volumes and quasi-static volume-pressure relationships in 22 normal upright bonnet (Macaca radiata) and 12 rhesus (M. mulatta) monkeys. In comparison with interspecies pulmonary function/body weight regressions our monkeys' lung volumes are larger and their lungs are considerably more compliant, but their chest wall compliance is similar to a wide range of mammalian species. However, chest wall compliance of our monkeys was found to be considerably less than that of other more commonly used experimental mammals such as dogs, cats, and rodents. The monkey chest walls were found to be about four times as stiff (3.3 +/- 0.1 (ml/cmH2O)/kg), whereas their lungs were nearly twice as compliant (9.2 +/- 0.7 (ml/cmH2O)/kg) compared to those of supine beagle dogs. Thus, their stiff chest wall sets their functional residual capacity (64.1 +/- 1.2% TLC30) at a much larger percentage of total lung capacity (TLC30) than that of the supine beagle dog (33.8% TLC30). Residual volume (13.2 +/- 1.9% TLC30) equaled the trapped gas volume after bilateral thoracotomy and was set by airway closure. We found more hysteresis area in the chest wall than in the lungs. Our measurements indicate that the static mechanical behavior of the respiratory system of the monkey compares well to man and that the monkey has considerable merit as an animal model for human respiratory function and disease research.