As the medical education curriculum is changing, it is still good to train students and physicians in many different patient locations.

Medical teaching methods are changing with students now encouraged to be self-learners, accruing more knowledge themselves, receiving less didactic instruction, utilizing more peer group interactions, and using more portable self-accessible technology to get medical information. Medical school curriculums are adapting with more simulated instruction, group analysis of clinical problems (problem-based learning), earlier exposure to patients and their evaluation, volunteer medical missions, and participation in relevant clinical research. But will these changes, especially the use of portable technology for retrieving medical information, enhance learning, and improve devising clinical strategy? To build clinical skills and confidence, it still seems relevant for the students and clinicians to evaluate patients in multiple locations under various circumstances. This is perhaps necessary during all phases of medical study, post-graduate training, research investigation, and in a medical career, including later phases when senior and elder faculty participate in medical teaching and/or provide health care. The emphasis of this perspective is to assess some of these clinical "settings" that reinforce learning skills and flexible clinical approaches.

Various approaches to clinically related research can yield helpful insight. A personal perspective.

Attending two recent meetings (the joint American Physician Scientists Association, American Society of Clinical Investigation, and Association of American Physicians meeting and the American Thoracic Society meeting) and listening to state of the art presentations, viewing research posters, and interacting with young scientists about so much new and exciting human research rekindled my thoughts about how one could now begin research. For me this occurred, with excellent mentoring and supervision, as first a descriptive "looking" approach to identify host immunity components in a variety of animal models and then manipulating these models to mimic disease processes, focusing on the respiratory tract and innate immunity. Next, we moved to characterize these host immunity components in normal humans, before applying these to in vitro and clinical illness situations for patients. The intent of this research sequence was to better describe and manipulate immunopathology relevant to disease. A bench-to-patient approach, mostly descriptive and "looking," was the path. I have illustrated these steps with applicable references. Now seems such a crucial time to further scientific knowledge and to foster personalized medicine, despite a period of financial restraint. We need discussion of ways to best approach "looking" for still unknown basic information about the human respiratory system. Two special examples are identifying the still unknown cells in human lung tissue and their functions and manipulating the extensive respiratory microbiome.

Bronchoalveolar lavage and other methods to define the human respiratory tract milieu in health and disease.

During fiber-optic bronchoscopy (FOB), surface sampling of the human respiratory airways and alveolar unit can be done with bronchoalveolar lavage (BAL), plus selective sites can be brushed for cells and transbronchial biopsies made in adjacent tissue. This permits analysis of the respiratory tract's milieu in healthy normals, in those with disease, and in control subjects. These combined procedures have been an established approach for obtaining specimens for research and for clinical assessment for over four decades. However, now new less invasive sampling methods are emerging. This review emphasizes BAL and the cellular and noncellular components recovered in fluid that have contributed to improving knowledge of how the respiratory tree's innate immunity can protect, and how airway structures can become deranged and manifest disease. After a discussion of training for FOB and procedural issues, a spectrum of respiratory diseases studied with BAL is presented, including airway illness (asthma and chronic obstructive pulmonary disease), diffuse interstitial lung diseases [idiopathic pulmonary fibrosis, rheumatoid interstitial lung disease (ILD), granulomatous ILDs], lung infections, lung malignancy, and upper and lower tract airway problems. Some recent studies with exhaled breath condensate analyses are given.

Workshop on idiopathic pulmonary fibrosis in older adults.

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary research, but these efforts have great potential to improve care for patients with IPF.

Free medical clinics: helping indigent patients and dealing with emerging health care needs.

An innovative movement of free medical clinics, which began in the 1960s, has helped indigent people without access to traditional health care. In this article, the author relates his experiences at three free clinics. Aside from the delivery of good care to deserving people, these clinics also had an impact on other relevant issues in medicine: The first of these clinics became involved with a chronic illness that affected medical research, the second provided another venue for medical teaching, and the third increased volunteerism, especially among senior clinicians. These secondary features are the focus of this article. The first clinic, created in a time of troubling social change, cared for many young people with infections, probably including some who were part of an evolving epidemic that was only later recognized as HIV/AIDS. The second clinic began when the traditional hospital and outpatient clinic settings for teaching medical students-both in their preclinical years and during clerkship rotations-were not conducive to learning the skills of interviewing and physical examination of cooperative patients. The more informal, less frenetic pace of a free clinic appealed to students and some residents as a place to build clinical skills. The new Liaison Committee on Medical Education standard to provide student service learning may formalize the use of free clinics in medical schools. The third clinic, like any of the 1,200 or more free clinics in the United States, cares for indigent people who have no access to established health care. The free clinic movement, which can provide some of the needed care, relies on volunteer physicians, many of whom are older and retired clinicians, who find that their contribution to free clinic care can be both useful to the patients and most rewarding to themselves.

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.

Present status of bronchoalveolar lavage in interstitial lung disease.

PURPOSE OF REVIEW: Sampling the detachable cells and acellular lining secretions of the human respiratory tract by bronchoalveolar lavage (BAL) is a means of obtaining relevant components from the airways and alveolar areas for research use and clinical analysis in normals (controls) and patients with a wide spectrum of interstitial lung diseases (ILDs). This review attempts to discuss recent findings from BAL studies that provide insight into pathogenic mechanisms of ILDs and/or assist in diagnosing disease activity. RECENT FINDINGS: BAL analysis and usefulness are reviewed for the major forms of ILDs. In addition, some perspective about this sampling method is given and the context for BAL is provided for the respective disease, either for diagnosis or research use. SUMMARY: Whereas BAL findings continue to impact on understanding disease pathogenesis and this may be its major use now, BAL fluid components, cells in particular, are not correlated well with activity of disease nor for monitoring disease progress or response to treatment. For a few rarer ILDs, BAL fluid characteristics may strongly support a diagnosis.

Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function.

The purpose of the workshop was to identify still obscure or novel cellular components of the lung, to determine cell function in lung development and in health that impacts on disease, and to decide promising avenues for future research to extract and phenotype these cells. Since robust technologies are now available to identify, sort, purify, culture, and phenotype cells, progress is now within sight to unravel the origins and functional capabilities of lung cells in developmental stages and in disease. The Workshop's agenda was to first discuss the lung's embryologic development, including progenitor and stem cells, and then assess the functional and structural cells in three main compartments of the lung: (1) airway cells in bronchial and bronchiolar epithelium and bronchial glands (basal, secretory, ciliated, Clara, and neuroendocrine cells); (2) alveolar unit cells (Type 1 cells, Type 2 cells, and fibroblasts in the interstitium); and (3) pulmonary vascular cells (endothelial cells from different vascular structures, smooth muscle cells, and adventitial fibroblasts). The main recommendations were to: (1) characterize with better cell markers, both surface and nonsurface, the various cells within the lung, including progenitor cells and stem cells; (2) obtain more knowledge about gene expression in specific cell types in health and disease, which will provide insights into biological and pathologic processes; (3) develop more methodologies for cell culture, isolation, sorting, co-culture, and immortalization; and (4) promote tissue banks to facilitate the procurement of tissue from normal and from diseased lung for analysis at all levels.

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.

In choosing a research health career, mentoring is essential.

An academic career in medical research can be wonderfully rewarding if the new biologic and health knowledge one discovers is later translated into the design of better health care strategies or clinical therapy. With so many new investigative methods available, this seems to be an opportune time to enter the research field. However, the seemingly limitless possibilities for discovery might not be realized if an ample new investigator work force is not maintained. Preparing and training young investigators are included in the primary mission of the National Institutes of Health (NIH),which is to support and facilitate scientific research. The National Heart, Lung, and Blood Institute (NHLBI) is very involved in research training, as are the professional pulmonary societies, patient disease-related organizations, and pharmaceutical companies who support this partnership. This perspective will review ways, young students initially may become interested in science and perhaps medicine through the help of mentors, and exposure to early research opportunities that allow them to experience the excitement of science. Then, later career development strategies will be presented that might further the interest of undergraduate and young health professionals to pursue medical research. As creative and spirited mentoring efforts are often very important in career selection, current approaches need to be critiqued for improvement.

Medical volunteering: giving something back.

A national health issue is how to provide medical care for the large number of people who are uninsured or do not qualify for medical coverage. Establishing free health clinics staffed by volunteer health professionals is one approach that is increasing, but this alone will not solve this societal problem. Many volunteer health care providers are needed, and more senior and retired physicians might be recruited. However, practicing general, not subspeciality, medicine in an unfamiliar surrounding with different patient demands may seem intimidating and anxiety producing. However, a conducive clinical environment and working with other volunteer health care staff may alleviate these feelings and make medical volunteering very enjoyable. The Mercy Health Clinic in Montgomery County, Maryland, has had this effect on us who volunteer there and care for its needy patients.

Lung transplantation: opportunities for research and clinical advancement.

Lung transplantation is the only definitive therapy for many forms of end-stage lung diseases. However, the success of lung transplantation is limited by many factors: (1) Too few lungs available for transplantation due to limited donors or injury to the donor lung; (2) current methods of preservation of excised lungs do not allow extended periods of time between procurement and implantation; (3) acute graft failure is more common with lungs than other solid organs, thus contributing to poorer short-term survival after lung transplant compared with that for recipients of other organs; (4) lung transplant recipients are particularly vulnerable to pulmonary infections; and (5) chronic allograft dysfunction, manifest by bronchiolitis obliterans syndrome, is frequent and limits long-term survival. Scientific advances may provide significant improvements in the outcome of lung transplantation. The National Heart, Lung, and Blood Institute convened a working group of investigators on June 14-15, 2004, in Bethesda, Maryland, to identify opportunities for scientific advancement in lung transplantation, including basic and clinical research. This workshop provides a framework to identify critical issues related to clinical lung transplantation, and to delineate important areas for productive scientific investigation.

Investigative bronchoprovocation and bronchoscopy in airway diseases.

RATIONALE: Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to collect biological specimens and tissue, perhaps with added bronchoprovocation in asthma syndromes. These procedures have yielded a wealth of important scientific information. Since the last critical review more than a decade ago, some of the techniques and applications have changed, and untoward events have occurred, raising safety concerns and increasing institutional review scrutiny. OBJECTIVES AND METHODS: To reappraise these investigational methods in the context of current knowledge, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a working group to review these procedures used for airway disease research, emphasizing asthma and chronic obstructive pulmonary disease. MAIN RESULTS: The group reaffirmed the scientific importance of investigative bronchoscopy and bronchoprovocation, even as less invasive technologies evolve. The group also considered the safety of bronchoscopy and bronchoprovocation with methacholine and antigen to be acceptable for volunteer subjects and patients, but stressed the need to monitor this closely and to emphasize proper training of participating medical research personnel. Issues were raised about vulnerable volunteers, especially children who need surrogates for informed consent. CONCLUSION: This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States.

Interstitial lung diseases--where we started from and are now going.

BACKGROUND AND AIM: Research into mechanisms causing interstitial lung diseases (ILD) began 35 years ago with the advent of cellular immunology and techniques to sample airways for biologic materials. After an analysis of lung research programs by the then National Heart and Lung Institute in 1972 identified as a priority the study of fibrotic and immunologic lung diseases, this began in the Pulmonary Branch (1974) of the Institute's intramural program. The Division of Lung Diseases initiated extramural research support also. ILD research developed quickly at many centers in the US and throughout the world. This review focuses on idiopathic pulmonary fibrosis (IPF) and highlights some of the initial research from the Pulmonary Branch. RECENT RESEARCH PARADIGM: In the 1990s research emphasis changed from a focus on inflammation to alveolar epithelial injury, fibrogenesis in fibroblastic foci, myofibroblast function, cytokine secretion and disordered matrix remodeling. More precise classification of ILD was advocated, especially for IPF. New strategies for therapy of IPF followed, including anti-fibrotic agents and interferon gamma treatment. However, therapy is still not sufficiently effective. Much is still left to do. FUTURE DIRECTIONS: The NHLBI research support continues for ILD, especially IPF. Current programs include: searching for new molecular therapeutic targets; establishing of a clinical network for IPF patients to assess combinations of therapy and new agents as appropriate; identifying genomic and genetic susceptibility factors; and creating a repository for lung tissue and biologic samples to aid investigators.

The mysterious pulmonary brush cell: a cell in search of a function.

Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of the epithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (approximately 120-140/cell) on the cell surface. The microvilli contain filaments that stretch into the underlying cytoplasm. They have a distinctive pear shape with a wide base and a narrow microvillous apex. The function of the pulmonary brush cell is obscure. For this reason, a working group convened on August 23, 2004, in Bethesda, Maryland, to review the physiologic role of the brush (microvillous) cell in normal airways and alveoli and in respiratory diseases involving the alveolar region (e.g., emphysema and fibrosis) and airway disease characterized by either excessive or insufficient amounts of airway fluid (e.g., cystic fibrosis, chronic bronchitis, and exercise-induced asthma). The group formulated several suggestions for future investigation. For example, it would be useful to have a panel of specific markers for the brush cell and in this way separate these cells for culture and more direct examination of their function (e.g., microarray analysis and proteomics). Using quantitative analysis, it was suggested to examine the number and location of the cells in disease models. Understanding the function of these cells in alveoli and airways may provide clues to the pathogenesis of several disease states (e.g., cystic fibrosis and fibrosis) as well as a key for new therapeutic modalities.