Medicina pulmonar y respiratoria

Recently a great deal of progress has been made in our understanding of pulmonary hypertension (PH). Research from the past 30 years has resulted in newer treatments that provide symptomatic improvements and delayed disease progression. Unfortunately, the cure for patients with this lethal syndrome remains stubbornly elusive. With the relative explosion of scientific literature regarding PH, confusion has arisen regarding animal models of the disease and their correlation to the human condition. This short review uniquely focuses on the clear and present need to better correlate mechanistic insights from existing and emerging animal models of PH to specific etiologies and histopathologies of human PH. A better understanding of the pathologic processes in various animal models and how they relate to the human disease should accelerate the development of newer and more efficacious therapies.

Behçet's disease is a multisystem vasculitis of unknown etiology. Thoracic lesions are dominated by venous and arterial diseases. We identified 21 cases with a hospital prevalence of Behçet's disease between January 1997 and June 2012. The prevalence was of 0.2%. Hemoptysis was the most common symptom and superior vena cava syndrome was the most common sign. Chest Computerized Tomography (CT) scan had confirmed thrombosis of the superior vena cava in 15 patients, and the pulmonary artery aneurysms in 6 patients, three of them were complicated by thrombosis. Patients followed for thrombosis of the superior vena cava received anticoagulant therapy, corticosteroid and immunosuppressive. The combination of corticosteroids, colchicine and immunosuppressive drugs was prescribed in patients with pulmonary aneurysms before surgical treatment. The authors concluded through this study for the rarity and severity of thoracic manifestations of Behçet's disease. Therapeutic means are limited and the prognosis is poor. Thoracic lesions of Behçet's disease are not rare in Mediterranean countries, diagnosis is easy with CT scan, but there’s a late in treatment. In these cases, prognosis is conditioned by thoracic lesions.

Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies.

Idiopathic Pulmonary Hemosiderosis is a rare condition, primarily affecting the pediatric population. IPH is characterized by the triad of hemoptysis, iron deficiency anemia, and diffuse pulmonary infiltrates, though not all the symptoms may be seen. Due to the myriad of diseases that present as such, IPH is often a diagnosis of exclusion. Treatment with corticosteroids prevents further episodes of hemoptysis, and improves the anemia. We report on a rare case of IPH in an adult who presented with chronic anemia and shortness of breath.

Sarcoidosis is an idiopathic multisystem disorder characterized by noncaseating epithelioid granulomas predominately affecting lungs and lymph nodes, but with potential to affect any organ system. Sarcoidosis shares similarities in development to other infectious granulomatous diseases, such as berylliosis and tuberculosis; however, its elusive etiology and non-distinctive histology have provided many diagnostic challenges. Evidence of a transferrable antigen combined with a high incidence rate in the lungs has focused efforts primarily on antigens with airborne transmissibility. While Mycobacterium tuberculosis and Propioni bacterium acnes have provided strong associations to implicate each as a contributor to sarcoidosis pathogenesis, detection challenges remain and consensus of a definitive antigen is lacking. Uncovering common polymorphisms has added another layer to the pathophysiology of sarcoidosis. Polymorphisms involving BTNL2, NODS, Notch and Anxa11, as well as certain HLA alleles, such as DRB1*0301 and DRB1*1101 may confer predisposition or resistance to sarcoidosis. Additionally, polymorphisms such as BTNL2 rs2076530 and Anxa11 rs1049550 show efficacy in increasing susceptibility or have no effect in certain ethnic groups. These polymorphisms also show familial linkages and may provide markers for disease severity. Without definitive diagnostic criteria, sarcoidosis remains a multistep diagnosis of exclusion. Therapeutics has improved clinical management of sarcoidosis while providing an avenue to further elucidate a possible antigen. While corticosteroids are often used as a first line of defense, unacceptable side effects may occur, leading to the implementation of alternative therapeutics. Alternatively, Disease Modifying Anti-Rheumatic Drugs, antimalarial drugs, Tumor Necrosis Factor Alpha (TNF-α) antagonists and antimicrobial drugs have recently been implemented with beneficial results. In this review we discuss potential causative antigens, diagnostic challenges associated with sarcoidosis and review current therapeutics.

Background: To investigate whether the extent of emphysema, visually confirmed by high resolution computed tomography (HRCT) in patients with COPD were associated with different indices of lung functions.

Methods: Eighty-two patients with COPD underwent HRCT scanning; visual assessment of HRCT scan was used in the calculation of extent of emphysematous

Destruction: The patients were clinically stable at the time of the evaluation. All subjects were smokers or past smokers who had smoked>10 pack-years.

Results: The mean visual emphysema score in all patients was 2.21 ± 1.11. While the mean emphysema score in patients with COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 3 was 2.88 ± 1.03, it was 1.54 ± 1.16 in COPD GOLD stage 2 (p<0.001). There was a significant correlation between the emphysema score and the numbers of pack/years smoked (R=0.58, p<0.001). The visual emphysema score was inversely correlated with the FEV1(r =-0.56, p<0.0001), FVC (r=-0.38, p=0.001), FEV1/FVC (r=-0.43, p<0.001), PEF(r=-0.44, p<0,001) and with the Carbon monoxide diffusing capacity divided by the alveolar volume (DLCO/VA) (r=-0.50, p<0.001). In our study population, patients had a limited expression of the disease as represented by low scores in Saint George Respiratory Questionnaire (SGRQ), and there was no correlation between emphysema score and SGRQ.

Conclusions: HRCT visual scores correlated with functional indices of airflow obstruction and impaired lung diffusing capacity in patients with stable COPD of varying severity, the presence of pulmonary emphysemais best represented by the FEV1 and DLCO/VA.

The common causes of mediastinal mass are neoplasms including Hodgkin’s disease, neuroblastoma and non- Hodgkin’s lymphoma. About one third of the cases are benign such as teratomas, neurofibromas and lipomas. Histological findings are essential to distinguish between benign and malignant conditions. Zygomycosis is a rare fungal infection usually presenting as a subcutaneous infection. Visceral involvement is reported usually with pulmonary and gastrointestinal tract involvement. Here the authors report a case of zygomycosis in an immunocompetent adult male who presented with mediastinal mass.

Background: Olodaterol is a once-daily long-acting β2-agonist being investigated for the treatment of chronic obstructive pulmonary disease, with ≥ 24 hour bronchodilator activity.

Methods: Two replicate, randomized, double-blind, four-way crossover (6-week treatment periods), active (tiotropium 18 μg via HandiHaler®)- and placebo-controlled trials were conducted to evaluate the 24 hour forced expiratory volume in 1 second (FEV1) profile of olodaterol (5 and 10 μg) once daily (via Respimat®). Patients continued with inhaled corticosteroids and xanthines. Spirometry was performed at baseline and over the entire 24 hour post-dose period at week 6 of each treatment phase. Co-primary end points were change from study baseline (response) in FEV1 area under the curve from 0–12 hours (AUC0–12) and FEV1 AUC from 12–24 hours (AUC12– 24); key secondary end point was FEV1 AUC from 0–24 hours response.

Results: In study 1222.39, there was a significant difference from placebo in FEV1 AUC0–12 and AUC12–24 responses (P<0.0001) with olodaterol 5 μg (0.185 and 0.131 L) and 10 μg (0.207 and 0.178 L) at 6 weeks; similar results were observed for tiotropium (0.173 and 0.123 L). In study 1222.40, responses were 0.197 and 0.153 L with olodaterol 5 μg, 0.221 and 0.170 L with 10 μg, and 0.221 and 0.164 L with tiotropium versus placebo (P<0.0001). Incidence of adverse events was comparable across treatments.

Conclusions: These data confirm the 24 hour lung-function efficacy profile of once-daily olodaterol, with FEV1 responses comparable to tiotropium.