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BACKGROUND The National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) provided a structured review of cases in which there was uncertainty or disagreement regarding diagnosis or clinical event classification. This article describes the diagnosis and adjudication processes. METHODS The diagnostic process was based on review of clinical data and high-resolution CT scans with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. The AC used a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures. RESULTS The IPFnet trials screened 1,015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. The AC reviewed 88 suspected acute exacerbations (AExs), 93 nonelective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators, as necessary clinical data were often not collected, particularly when subjects were evaluated outside of the primary study site. CONCLUSIONS The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early because of safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AExs and hospitalizations as outcome measures. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00517933, NCT00650091, NCT00957242; URL: www.clinicaltrials.gov

OBJECTIVE Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH.

Background An evidence-based approach is necessary for the localization and management of intraepithelial and microinvasive non-small cell lung cancer in the central airways. Methods Material appropriate to this topic was obtained by literature search of a computerized database. Recommendations were developed by the writing committee and then reviewed by the entire guidelines panel. The final recommendations were made by the Chair and were voted on by the entire committee. Results White light bronchoscopy has diagnostic limitations in the detection of microinvasive lesions. Autofluorescence bronchoscopy (AFB) is a technique that has been shown to be a sensitive method for detecting these lesions. In patients with moderate dysplasia or worse on sputum cytology and normal chest radiographic findings, bronchoscopy should be performed. If moderate/severe dysplasia or carcinoma in situ (CIS) is detected in the central airways, then bronchoscopic surveillance is recommended. The use of AFB is preferred if available. In a patient being considered for curative endobronchial therapy to treat microinvasive lesions, AFB is useful. A number of endobronchial techniques as therapeutic options are available for the management of CIS and can be recommended to patients with inoperable disease. In patients with operable disease, surgery remains the mainstay of treatment, although patients may be counseled about these techniques. Conclusions AFB is a useful tool for the localization of microinvasive neoplasia. A number of endobronchial techniques available for the curative treatment can be considered first-line therapy in inoperable cases. For operable cases, the techniques may be considered and discussed with the patients.

Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence.This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus.Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded.Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH.

Background: Although airway angiogenesis and edema have been proposed to contribute to the airway remodeling process in patients with asthma, there are few studies looking at these structural components in the airway tissue of asthma patients. Mycoplasma infection may be associated with chronic asthma and has been shown to induce angiogenesis and edema in a murine model. Participants and measurements: We evaluated blood vessels and edema by immunohistochemistry in endobronchial biopsy samples from 10 normal control subjects and 15 patients with mild-tomoderate asthma before and after a 6-week treatment with clarithromycin (n 5 8) or placebo (n 5 7). Type IV collagen and a2-macroglobulin were used to identify blood vessels and edema in the tissue, respectively. Mycoplasma pneumoniae was evaluated by polymerase chain reaction. Setting: National Jewish Medical and Research Center. Results: At baseline, the vascularity, the number of blood vessels, and the edematous area in the airway tissue were not significantly different between asthmatic patients and normal control subjects. However, asthmatic patients demonstrated increased blood vessel size compared with normal control subjects (p 5 0.03). After clarithromycin treatment in asthmatic patients, the number of blood vessels was increased (p 5 0.02), while edema decreased (p 5 0.049). Asthmatic patients who tested positive for M pneumoniae showed a significant increase in vascularity than asthmatic patients who tested negative for M pneumoniae (p 5 0.02). Conclusion: Our data suggest that angiogenesis and edema may not be significant features of airway remodeling in patients with chronic, mild-to-moderate asthma. Clarithromycin treatment in asthmatic patients could reduce the edematous area as identified by a2-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels. (CHEST 2001; 119:416 ‐ 422)

Bronchial intraepithelial lesions may be precursors of central airway lung carcinomas. Identification and early treatment of these preinvasive lesions might prevent progression to invasive carcinoma.We systematically reviewed the literature to develop evidence-based recommendations regarding the diagnosis and treatment of intraepithelial lesions.The risk and timeline for progression of bronchial intraepithelial lesions to carcinoma in situ (CIS) or invasive carcinoma are not well understood. Multiple studies show that autofluorescence bronchoscopy (AFB) is more sensitive that white light bronchoscopy (WLB) to identify these lesions. In patients with severe dysplasia or CIS in sputum cytology who have chest imaging studies showing no localizing abnormality, we suggest use of WLB; AFB may be used as an adjunct when available. Patients with known severe dysplasia or CIS of central airways should be followed with WLB or AFB, when available. WLB or AFB is also suggested for patients with early lung cancer who will undergo resection for delineation of tumor margins and assessment of synchronous lesions. However, AFB is not recommended prior to endobronchial therapy for CIS or early central lung cancer. Several endobronchial techniques are recommended for the treatment of patients with superficial limited mucosal lung cancer who are not candidates for resection.Additional information is needed about the natural history and rate of progression of preinvasive central airway lesions. Patients with severe dysplasia or CIS may be treated endobronchially; however, it remains unclear if these therapies are associated with improved patient outcomes.

This prospective study was done to determine whether immediate echocardiography, to implicate or exclude a cardiac basis for breathlessness, can improve the management of acute dyspnea. One hundred ninety-six consecutive patients admitted to the hospital with a chief complaint of dyspnea were randomized to receive or not receive an echocardiogram within 24 hours of admission. Most patients randomized to echo and control groups had cardiac or pulmonary disease and were comparable in their other clinical characteristics. Predefined study end points included the following: change in diagnosis or treatment; performance of additional diagnostic cardiopulmonary studies; and duration of hospitalization (the principal end point). Changes in diagnosis or treatment during hospitalization were as infrequent among patients randomized to echo as among control patients. Echocardiography independently confirmed the clinical diagnosis in 72 percent of echo-randomized patients. Even when echo findings conflicted with the clinical diagnosis, the diagnosis and management plan rarely changed. Additional cardiac or pulmonary studies were ordered as frequently among patients randomized to echocardiography as among those randomized to control. The mean duration of hospital stay also did not differ between the two groups, and no clinical parameter served to predict which subgroup of patients might benefit from echocardiography. Although echocardiography can be expeditiously obtained during respiratory exacerbations of cardiopulmonary disease, indiscriminate echo does not necessarily hasten or alter the treatment of such patients.

Although airway angiogenesis and edema have been proposed to contribute to the airway remodeling process in patients with asthma, there are few studies looking at these structural components in the airway tissue of asthma patients. Mycoplasma infection may be associated with chronic asthma and has been shown to induce angiogenesis and edema in a murine model.We evaluated blood vessels and edema by immunohistochemistry in endobronchial biopsy samples from 10 normal control subjects and 15 patients with mild-to-moderate asthma before and after a 6-week treatment with clarithromycin (n = 8) or placebo (n = 7). Type IV collagen and alpha(2)-macroglobulin were used to identify blood vessels and edema in the tissue, respectively. Mycoplasma pneumoniae was evaluated by polymerase chain reaction.National Jewish Medical and Research Center.At baseline, the vascularity, the number of blood vessels, and the edematous area in the airway tissue were not significantly different between asthmatic patients and normal control subjects. However, asthmatic patients demonstrated increased blood vessel size compared with normal control subjects (p = 0.03). After clarithromycin treatment in asthmatic patients, the number of blood vessels was increased (p = 0.02), while edema decreased (p = 0.049). Asthmatic patients who tested positive for M pneumoniae showed a significant increase in vascularity than asthmatic patients who tested negative for M pneumoniae (p = 0.02).Our data suggest that angiogenesis and edema may not be significant features of airway remodeling in patients with chronic, mild-to-moderate asthma. Clarithromycin treatment in asthmatic patients could reduce the edematous area as identified by alpha(2)-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels.

Objective: The aim of the study was to assess the diagnostic yield of the real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis and staging of lung cancer. Patients and methods: 134 patients with suspected lung cancer with mediastinal and/or hilar lymph nodes underwent EBUS-TBNA using the convex probe EBUS. All patients with negative EBUS-TBNA subsequently underwent the surgery or mediastinoscopy as a confirmatory test. Results: One hundred thirty four patients underwent CP-EBUS-TBNA between December 2007 to December 2009. There were 233 mediastinal & hilar lymph nodes biopsied (stations: 2R-3,4R-73, 4L-21, 7-65, 10R-23, 10L-5, 11R-26, 11L-17). EBUS-TBNA revealed metastatic lymph node involvement in 54 of 134 patients (40.3%) and in 56 of 233 biopsies (24%). In 80 patients with negative or uncertain EBUS-TBNA who underwent subsequent surgery, mediastinoscopy, metastatic nodes were diagnosed in four patients (3%) in stations: (4R-2,4L-1 & 7-1). The false-negative results of biopsies were found only in small nodes