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Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease resulting from inhalational exposure to any of a large variety of antigens. A subgroup of patients with HP develops pulmonary fibrosis (fibrotic HP; FHP), a significant cause of morbidity and mortality. This study will evaluate the safety and efficacy of the antifibrotic pirfenidone in treating FHP. This single-centre, randomised, double-blind, placebo-controlled trial is enrolling adults with FHP (ClinicalTrials.gov: NCT02958917). Study participants must have fibrotic abnormalities involving ≥5% of the lung parenchyma on high-resolution computed tomography scan, forced vital capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised in a 2:1 ratio to receive pirfenidone 2403 mg·day−1 or placebo. The primary efficacy end-point is the mean change in FVC % predicted from baseline to week 52. A number of secondary end-points have been chosen to evaluate the safety and efficacy in different domains., The design of a phase II study of 52 weeks of pirfenidone or placebo on top of standard of care in patients with fibrotic HP (ClinicalTrials.gov NCT02958917) https://bit.ly/32CfeSF

Objective: To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). Patients and Methods: We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. Diagnostic yield was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. Clinical utility was defined as a biopsy result deemed useful in patient management. Results: The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; P=.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; P=.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; P=.010 and OR, 3.23; 95% CI, 1.76 to 6.10; P

Background Thrombolytic therapy is widely accepted for massive pulmonary embolism (PE) due to the high mortality risk associated with standard anticoagulation alone. Its role in submassive PE, however, has remained controversial. We aimed to evaluate whether the selective use of systemic thrombolytic therapy with intravenous tissue plasminogen activator (IV-tPA) improves the survival of patients with submassive PE at increased risk for clinical deterioration. Methods A total of 184 consecutive patients diagnosed with acute PE by chest thoracic angiography (CTA) were included in a retrospective study. Pulmonary artery obstruction and right/left ventricular dysfunction were evaluated by CTA and echocardiography. Medical history and simplified PE Severity Index (sPESI) were assessed at diagnosis. Hemodynamic and respiratory status were recorded at diagnosis, admission to pulmonary unit and prior to thrombolytic therapy. Patient survival was assessed at 30 of 90 days from diagnosis by CTA. Results All low risk patients (36%) per sPESI survived. Among the 117 remaining patients, 31% received IV-tPA. Respiratory failure was associated with decreased age-adjusted survival (P = 0.005). Among patients with respiratory failure selected for IV-tPA, age-adjusted survival was improved significantly compared to others (P = 0.043). Conclusions Thrombolytic therapy for hemodynamically stable PE patients with respiratory failure may improve survival. Trial registration MMC-0216-14

Case Presentation We present the case of a 48-year-old South African woman with no smoking history, and seropositive rheumatoid arthritis diagnosed in 2001. She was treated with chloroquine (150 mg, 4 times per week) and methotrexate (30 mg weekly) with well-controlled symptoms until 2015, when she developed a disease flare. Her treatment regimen was changed to leflunomide (20 mg daily) monotherapy with subsequent symptom control. Biologic agents were not accessible because of cost constraints.

Interstitial lung disease (ILD) associated with connective tissue diseases (CTDs) is highly heterogeneous in its clinical presentation and course. The diagnosis and management of CTD-ILD require a multidisciplinary approach involving, at minimum, a rheumatologist, a pulmonologist, and a radiologist. Close monitoring of patients with CTD-ILD is important to enable early detection of disease progression and inform decisions regarding the initiation or escalation of pharmacotherapy. In the absence of guidelines regarding how CTD-ILDs should be treated, clinicians face difficult decisions on when to use immunosuppressant and anti-fibrotic therapies. The importance of a multidisciplinary and individualized approach to the diagnosis and management of CTD-ILD is highlighted in the three case studies that we describe in this article.

Sjogren's syndrome is associated with chronic cough, but sicca symptoms are missing from cough evaluation guidelines. We evaluated patients with unexplained cough for undiagnosed Sjogren's syndrome. Patients referred to our pulmonary clinic (Sheba Medical Center, 2009 to 2012) with unexplained cough and concomitant dry eyes were selected for evaluation. Unexplained cough was defined as chronic cough of unknown etiology despite algorithm-based evaluation and treatment. Patients were evaluated in a dedicated clinic by a pulmonologist, rheumatologist, and ophthalmologist specializing in autoimmune disease. Patients completed the Leicester Cough Questionnaire, spirometry, antibody testing for anti Ro/La, ophthalmologic examination with visual acuity, eyelid, ocular surface fluorescein staining, tear break-up time and Schirmer's test, full slit lamp, and fundus examinations. Four-year follow-up was conducted by telephone questionnaire. We identified 24 patients among which 22 (21 females) agreed for evaluation. Eight patients (36%), seven initially, and one during follow-up were diagnosed with Sjogren's syndrome (SS) (six secondary and two primary SS). At 4-year follow-up, cough tended to persist and improve in only 37% with SS. These include 2 (Scl and RA) who received rituximab and 1 (stage 1 sarcoidosis) with spontaneous improvement. In contrast, cough improved in most (64%) patients without SS; the majority (eight/nine) report intensified disease-specific treatment (five allergic and three GERD). We describe patients in whom unexplained chronic cough was associated with dry eyes. Focused workup revealed undiagnosed Sjogren's syndrome in 36%. Dry eyes, with or without SS, is under-recognized and should be added to diagnostic algorithms for unexplained cough.

A ground glass opacity (GGO) lung lesion may represent early stage adenocarcinoma, which has an excellent prognosis upon prompt surgical resection. However, GGO lesions have broad differential diagnoses, including both benign and malignant lesions. Our objective was to study telomere length and telomerase activity in patients with suspected lung cancer in which GGO was the predominant radiographic feature. Knowledge of telomere biology may help distinguish malignant from benign radiographic lesions and guide risk assessment of these lesions. Peripheral blood samples were taken from 22 patients with suspected adenocarcinoma with the GGO radiographic presentation. Multidisciplinary discussion confirmed the need for surgery in all cases. We used an age and gender‐matched group without known lung disease as a control. Telomere length and aggregates were assessed by quantitative fluorescence in situ hybridization (QFISH) and quantitative PCR. Cell senescence was evaluated by senescence‐associated heterochromatin foci. Subjects with GGO lesions had a higher percentage of lymphocytes with shorter telomeres (Q‐FISH, P = 0.003). Furthermore, relative telomere length was also reduced among the GGO cases (qPCR, P < 0.05). Increased senescence was observed in the GGO group compared to controls (P < 0.001), with significant correlation between the senescence‐associated heterochromatin foci and aggregate formation (r = −0.7 and r = −0.44 for cases and controls, respectively). In conclusion, patients with resectable early adenocarcinoma demonstrate abnormal telomere length and cell senescence in peripheral blood leukocytes compared to control subjects. Abnormal telomere biology in the peripheral blood may increase suspicion of early adenocarcinoma among patients with GGO lesions.

Yoram Neuman,1,3 Matthew Koslow,2,3 Alona Matveychuk,2,3 Avigdor Bar-Sef,1 Alexander Guber,2,3 David Shitrit2,3 1Division of Cardiology, 2Pulmonary Department, Meir Medical Center, Kfar Saba, Israel; 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Background and objective: Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB), but data concerning the degree of PH are often lacking. We investigated whether COPD patients with PH who undergo bronchoscopy are at greater risk for complications. Methods: This prospective study included 207 consecutive COPD patients undergoing FB. All underwent an echo-Doppler to evaluate pulmonary artery pressure on the day of the bronchoscopy procedure. Pulmonologists were blinded to the echocardiogram results. Results: A total of 167 patients (80.7%) had normal pulmonary pressure. The remaining 40patients (19.3%) had PH: 27 (13.0%) mild, eight (3.9%) moderate, and five (2.4%) severe. Noninvasive hemodynamic parameters between groups before and after FB were similar. Two patients with normal pulmonary pressure developed supraventricular tachycardia. None developed hemodynamically significant dysrhythmia. Bleeding episodes between groups in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) did not differ. PH patients who underwent BAL and TBB had decreased O2 saturation during the procedure compared with the non-PH group (23.5% vs 6.9%, P=0.033). No deaths were attributable to FB. Conclusion: PH is common among COPD patients undergoing FB. PH patients undergoing BAL and TBB are at higher risk of decreased O2 saturation than those without PH. Further studies should assess the risk among COPD patients with moderate-to-severe PH. Keywords: bronchoscopy, hypoxemia, pulmonary hypertension

The objective of this study was to identify clinical and imaging features that distinguish rheumatoid lung nodules from malignancy. We conducted a retrospective review of 73 rheumatoid patients with histologically-proven rheumatoid and malignant lung nodules encountered at Mayo Clinic, Rochester, MN (2001–2016). Medical records and imaging were reviewed including a retrospective blinded review of CT and PET/CT studies. The study cohort had a mean age of 67 ± 11 years (range 45–86) including 44 (60%) women, 82% with a smoking history, 38% with subcutaneous rheumatoid nodules, and 78% with rheumatoid factor seropositivity. Subjects with rheumatoid lung nodules compared to malignancy were younger (59 ± 12 vs 71 ± 9 years, p

Objective.Interstitial lung diseases (ILD) form a diverse group of parenchymal lung disorders. Currently, a multidisciplinary team (MDT) including pulmonologists, radiologists, and pathologists is the gold standard for ILD diagnosis. Recently, additional subtypes of connective tissue disease (CTD)-ILD with autoimmune features were defined, making the rheumatological assessment increasingly important. We aimed to assess the effect of adding a rheumatologist to the MDT for routine rheumatology assessment.Methods.A prospective study that assessed newly diagnosed ILD patients by 2 parallel blinded arms; all patients were evaluated by both MDT (e.g., history, physical examination, blood tests, pulmonary function tests, and biopsies, if needed) and a rheumatologist (e.g., history, physical examination, blood and serological tests).Results.Sixty patients were assessed with the mean age of 67.3 ± 12 years, 55% male, and 28% smokers. The rheumatological assessment reclassified 21% of the idiopathic pulmonary fibrosis as CTD. Moreover, the number of CTD-ILD with autoimmune features was increased by 77%. These included antineutrophil cytoplasmic antibody–associated vasculitis, antisynthetase syndrome, and IgG4-related ILD. Retrospectively, rheumatological evaluation could have saved 7 bronchoscopies and 1 surgical biopsy.Conclusion.Adding routine rheumatology assessments could significantly increase diagnostic accuracy and reduce invasive procedures.

Global Strategy for the Diagnosis, Management, and Prevention of COPD 2018 is a consensus report published periodically since 2001 by an international panel of health professionals from respiratory medicine, socioeconomics, public health, and education comprising the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The GOLD documents endeavor to incorporate latest evidence and expert consensus and are intended for use as "strategy documents" for implementation of effective care for chronic obstructive lung disease (COPD) on a global level. The GOLD 2018 report defines COPD as a "common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities, usually caused by significant exposure to noxious particles or gases," with the criteria of "persistent respiratory symptoms" being a new and controversial inclusion since 2017. With the availability of newer pharmacotherapy options, treatment recommendations are made on the basis of a review of the latest literature and directed by symptom burden and health care utilization. Apart from the change in definition, a major shift in the recommendations is the exclusion of severity of airflow limitation as one of the major factors in guiding therapy. We review the salient features of the GOLD 2018 document and provide commentary on features that merit further discussion based on our clinical experience and practice as well as literature review current as of February 2018.

Background: Patients with lung cancer undergoing surgical and medical treatment are at increased risk for pulmonary complications. The importance of routine broncoscopy procedure in populations with lung cancer has rarely been defined. We aimed to determine the growth of potentially pathogenic microorganisms (PPM) among patients evaluated by bronchoscopy for lung cancer. Methods: This prospective study included 155 consecutive patients with lung mass or radiologic findings suspicious for malignancy. Baseline demographic, clinical and radiologic features were collected. Clinical features of infection were compared to microbiologic and histologic results. Results: The bacterial spectrum of lung cancer patients was similar to those without malignancy. The most frequently isolated organisms were Pseudomonas sp . and Staphylococcus aureus . Among all patients, bronchial bacterial positive PPM growth was noted in 30% (46/155). The significant PPM growth rate was three-fold higher among those with clinical signs of infection (P Conclusions: Bronchoscopic evaluations should include bacterial cultures for direct targeted antibiotic therapy only in the symptomatic patients.

Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.

To present the diagnostic accuracy and safety of a novel technique for CT-guided transthoracic needle aspiration biopsy (TNAB) of lung lesions suspected of malignancy.A novel technique for coaxial CT-guided TNAB is reported in this single-centre, retrospective study. A 22-gauge guide wire is used to accurately locate the lesion prior to biopsy. The technique enables penetration of lung lesions in various locations with less risk of harm to adjacent organs. Malignant and benign diagnoses were confirmed by histology or radiologic resolution.Clinical features of 181 patients included 59% men. Mean lesion size was 24 ± 14.9 mm with a mean depth of 13.6 ± 18.3 mm. Among 160 (88.4%) confirmed malignancies, 151 (94.4%) were diagnosed with TNAB. Among the 13 (7.2%) confirmed benign diagnoses, 11 (84.6%) received a specific, benign diagnosis with TNAB. The overall diagnostic accuracy of CT-TNAB was 93.6% among all confirmed diagnoses (173/181). Complications included 48 (26.5%) with pneumothorax, of which 77.8% resolved spontaneously, 20% by aspiration and 2.2% required chest drain insertion. Intrapulmonary haemorrhage was observed in 3.9% and hemoptysis in 6.0% without clinical significance.The guide wire technique provides a novel method for needle biopsy of lung lesions with improved accuracy and safety.Lung cancer screening has increased the detection of lung lesions. The guide wire technique is a novel method to biopsy lung lesions. The guide wire technique for lung biopsy demonstrates improved accuracy and safety. The chest tube insertion rate is reduced with aspiration during the procedure.

1.1 Imaging As previously described, the majority of patients with sarcoidosis are asymptomatic. The main reason patients seek medical attention is an abnormal imaging study. By far the most common situation is a chest radiography that was performed for an alternative diagnosis or as a routine procedure before anesthesia or surgery. In recent years the increased use of computed tomography (CT) in various screening programs for malignancy (colon, lung) or in cardiology has led to an explosion of “lung abnormalities,” many of which are eventually attributed to sarcoidosis. For example, 25% of solitary pulmonary nodules (SPN) on chest CT were attributable to “nonspecific granulomas” after tissue biopsy (Albert and Russell 2009). The recent report of the National Lung Screening Trial in USA favors a CT scan program for reducing the all cause mortality attributable to lung cancer (The National Lung Screening Trial Research Team 2011). This recommendation is expected to dramatically increase the number of chest CT examinations performed for screening purposes. It is likely that many of the abnormalities found in the lung parenchyma will undergo biopsy and be diagnosed as granulomatous sarcoid-like lesions. A practical approach to their management is needed. From a historical perspective, the suspicion of sarcoidosis is typically initiated by abnormal imaging. In fact, the pragmatic “Statement on Sarcoidosis” dedicates a subchapter to this issue in the “patient without histology” (Hunninghake et al. 1999). The authors claim that clinical and/or radiological features alone may be diagnostic for patients with stage I disease (98% reliability) or stage II (89% reliability), but less accurate for stage III (52% reliability). In a review of 100 patients with bilateral hilar lymphadenopathy, sarcoidosis was diagnosed if symptoms were limited to uveitis or erythema nodosum or in asymptomatic patients with a negative physical examination (74% of all patients). In these patients, the authors conclude that biopsy confirmation is not necessary.

OBJECTIVE: The clinical significance of vertebral osteomyelitis and infectious endocarditis co-infection is unclear. This study investigates the rate, clinical features, and outcome of vertebral osteomyelitis with and without concomitant infectious endocarditis. METHODS: A retrospective study of all cases of osteomyelitis with spinal imaging (n ¼ 176), from January 2007 to April 2013, that were diagnosed as vertebral osteomyelitis. Sixty-two patients with spontaneous vertebral osteomyelitis were identified after excluding postsurgical, decubitus ulcers and spinal metastases. Seventeen (27%) were identified with concomitant infectious endocarditis. RESULTS: All patients presented with back pain and 59% were diagnosed with infectious endocarditis subsequent to vertebral osteomyelitis. Distinguishing features among the co-infection group include the increased use of transesophageal echocardiography (94% vs 58%, P ¼ .004), predisposing cardiac conditions (59% vs 16%, P ¼ .001), and Gram-positive bacteremia, of which Streptococcus sp. and Enterococcus sp. were more common (35% vs 11%, P ¼ .026). Adverse neurologic events were increased significantly in the co-infection group (59% vs 22%, P ¼ .006). On transesophageal echocardiography, 88% of co-infection patients had highly mobile vegetations, 9 of which measured 10 mm or more. The overall mortality was 41% and 29% in the co-infection and lone vertebral osteomyelitis groups, respectively (P ¼ .356). One-year mortality was identical for both groups at 24% (P ¼ .999), and higher than previously reported (11.3% for lone vertebral osteomyelitis). CONCLUSIONS: Patients with vertebral osteomyelitis, in whom infectious endocarditis is not excluded, are at increased risk for adverse neurologic events and mortality. The prompt diagnosis of infectious endocarditis, and associated high-risk features that may benefit from surgical intervention, require early evaluation by transesophageal echocardiography.