Allergic diseases are most likely due to interactions between genetic and environmental factors. While many of the environmental components have been studied for years, only recently has significant progress been made in identifying the genes responsible for susceptibility or expression of these diseases. Genome-wide screens in various populations have identified the locations of susceptibility genes for asthma and atopy, as well as associated phenotypes such as bronchial hyperresponsiveness and increased total serum IgE levels. In addition, this positional cloning approach has led to the discovery of several genes for asthma or related phenotypes, which is extending our understanding of the pathophysiology of allergic diseases. As these genes are identified and characterized, the relationships of these genes to each other and the environment will become important areas of research. Understanding the basic interactions that lead to the development of allergy and asthma will lead to new therapeutic approaches that will be used to modify the development and clinical progression of these common disorders.

Pathologic and physiologic evidence has emerged in the last few years suggesting that the airway inflammation and remodeling that characterize asthma occur not only in the central airways but extend to the distal lung and the lung parenchyma. The distal airways are capable of producing T helper (Th) type 2 cytokines and chemokines, and, more recently, they have been recognized as a predominant site of airflow obstruction in asthmatic patients. In the lung parenchyma, a similar Th2 cytokine profile and infiltration of inflammatory cells also has been reported. The inflammation at this distal site has been described as being more severe when compared to the large amount of airway inflammation, and evidence of remodeling in the lung periphery is emerging. The recognition of asthma as a disease of the entire respiratory tract has an important clinical significance highlighting the need to also consider the distal lung as a target in any therapeutic strategy for effective treatment of this disease.

Interleukin (IL)-13 is a key cytokine in asthma pathogenesis. We used constitutive and inducible overexpression transgenic mice to characterize the mechanisms by which IL-13 causes phenotypic alterations in the lung. These studies demonstrated that chemokine receptor-2, transforming growth factor-beta(1), and IL-11 play an important role in the regulation of inflammation and remodeling in the IL-13-treated lung. The study results also demonstrated that IL-13 induces vascular endothelial growth factor, which causes bronchial circulation neovascularization in the murine airway. Last, it was demonstrated that IL-13 induces adenosine accumulation and that adenosine in turn stimulates IL-13 elaboration. These approaches validated in vivo genetic targets against which therapies can be directed to selectively regulate aspects of the IL-13 phenotype.

A woman at 23 weeks' gestation was treated with rifampin, isoniazid, and ethambutol for cavitary tuberculosis (TB). She did not respond within 3 weeks, and multidrug-resistant (MDR) TB was suspected. Direct plating on susceptibility media was performed immediately. Treatment was initiated with IV capreomycin, levofloxacin, para-aminosalicylic acid, pyrazinamide, cycloserine, and high-dose vitamin B(6) at 26 weeks' gestation. The patient delivered vaginally at week 35. The newborn was not infected. Following delivery, ethionamide was added as a sixth drug, and levofloxacin was replaced with moxifloxacin. The patient's sputum became smear-negative and culture-negative for TB. All reported cases of MDR-TB during pregnancy are reviewed.

To determine the effect of the addition of heliox to standard medical care on the course of acute asthma.

To evaluate, by systematic review, the efficacy of heliox on respiratory mechanics and outcomes in patients with acute asthma.

Intensivists are confronted with poisoned patients on a routine basis, with clinical scenarios ranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, or accidental exposure. In addition, drug toxicity can also manifest in hospitalized patients from inappropriate dosing and drug interactions. In this review article, we describe the epidemiology of poisoning in the United States, review physical examination findings and laboratory data that may aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) or specific poisoning, and describe a rational and systematic approach to the poisoned patient. It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. However, the most current recommendations by the American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists will be reviewed. Specific poisonings will be reviewed in the second section of these review articles.

Pulmonary involvement is common in patients with portal hypertension and can manifest in diverse manners. Changes in pulmonary arterial resistance, manifesting either as the hepatopulmonary syndrome or portopulmonary hypertension (PPHTN), have been increasingly recognized in these patients in recent years. This review summarizes the clinicopathologic features, diagnostic criteria, as well as the latest concepts in the pathogenesis and management of PPHTN, which is defined as an elevated pulmonary artery pressure in the setting of an increased pulmonary vascular resistance and a normal wedge pressure in a patient with portal hypertension.

Despite many years of clinical research, there is still no effective therapy for malignant pleural mesothelioma (MPM). Untreated, the prognosis is poor, with a median survival of < 1 year. Single-agent or combination chemotherapy as well as radiotherapy have not shown persistent improvements in response or survival. In general, MPM is a disease confined to the pleural cavity for a long time before metastasizing. Therefore, focus on local treatment seems rational. Surgical resection has been considered the mainstay of treatment by some. However, surgery alone results in high recurrence rates, and the survival benefit remains questionable. In recent years, the emphasis has been on surgery combined with adjuvant therapies. In this article, the present state of surgical management of MPM will be reviewed.

Several recent studies discuss bronchoscopic techniques for treating endobronchial lipoma, an extremely rare benign tumor.

Empyema is one of the potential complications of lower respiratory tract infections. Very rarely, in predisposed individuals, empyema can be caused by Trichomonas species, of which Trichomonas tenax appears to be the most common cause. Here, we present a case of trichomonal empyema in a 56-year-old man and review the available literature of this rare occurrence.

Castleman disease is an uncommon entity, most often occurring in patients presenting with localized mediastinal lymph node enlargement. While surgical resection is the preferred treatment, there are concerns about approaching this highly vascular tumor with thoracoscopy. We present the second reported case of thoracoscopic resection of a patient with Castleman disease and review the literature.

It is well established that macrolide antibiotics are efficacious in treating sinopulmonary infections in humans. However, a growing body of experimental and clinical evidence indicates that they also express distinct salutary effects that promote and sustain the reparative process in the chronically inflamed upper and lower respiratory tract. Unlike the anti-infective properties, these distinct effects are manifested at lower doses, usually after a relatively prolonged period (weeks) of treatment, and in the absence of an identifiable, viable pathogen. Long-term, low-dose administration of macrolide antibiotics has been used most commonly for sinusitis, diffuse panbronchiolitis, asthma, bronchiectasis, and cystic fibrosis. It is associated with down-regulation of nonspecific host inflammatory response to injury and promotion of tissue repair. Although large-scale trials are lacking, the prolonged use of these drugs has not been associated with emergence of clinically significant bacterial resistance or immunosuppression. Long-term, low-dose administration of 14- and 15-membered ring macrolide antibiotics may represent an important adjunct in the treatment of chronic inflammatory sinopulmonary diseases in humans.