Glucocorticoids are frequently used to treat patients with pulmonary diseases, but continuous long-term use of glucocorticoids may lead to significant bone loss and an increased risk of fragility fractures. Patients with certain lung diseases, regardless of pharmacotherapy-particularly COPD and cystic fibrosis-and patients waiting for lung transplantation are also at increased risk of osteoporosis. Fragility fractures, especially of the hip, will have substantial effects on the health and well-being of older patients. Vertebral collapse and kyphosis secondary to glucocorticoid-induced osteoporosis (GIO) may affect lung function. Identification of patients with osteopenia, osteoporosis, or fragility fractures related to osteoporosis is strongly recommended and should lead to appropriate treatment. Prevention of GIO in patients receiving continuous oral glucocorticoids is also recommended. In patients receiving either high-dose inhaled glucocorticoids or low- to medium-dose inhaled glucocorticoids with frequent courses of oral glucocorticoids, bone mineral density measurements should be performed to screen for osteopenia and osteoporosis. A bisphosphonate (risedronate or alendronate), calcium and vitamin D supplementation, and lifestyle modifications are recommended for the prevention and treatment of GIO.

Part 1: To describe cases of emphysema (subcutaneous and/or mediastinal) and pneumothorax after percutaneous dilational tracheostomy (PDT) in a series of 326 patients, and to review the existing literature describing the incidence and possible mechanisms. Part 2: To analyze the potential mechanisms for the development of emphysema and pneumothorax in human cadaver models.

The ECG is an indispensable tool in the ICU for the detection and diagnosis of heart disease. ECG abnormalities however can be present in a wide variety of noncardiac conditions, complicating the differential diagnosis with primary cardiac pathology. This overview discusses the ECG abnormalities and their pathophysiologic basis in the most frequently encountered noncardiac conditions, such as electrolyte abnormalities, pulmonary embolism, CNS diseases, esophageal disorders, hypothermia, and drug-related and other conditions. Knowledge of the characteristic ECG changes may provide early clues to the presence of these disorders, the prompt recognition of which can be life saving.

Nearly all hematologic malignancies can occasionally present with or develop pleural effusions during the clinical course of disease. Among the most common disorders are Hodgkin and non-Hodgkin lymphomas, with a frequency of 20 to 30%, especially if mediastinal involvement is present. Acute and chronic leukemias, myelodysplastic syndromes, are rarely accompanied by pleural involvement. Furthermore, 10 to 30% of patients receiving bone marrow transplantation develop pleural effusions. In cases of hematologic pleural effusions, drug toxicity, underlying infectious, secondary malignant or rarely autoimmune causes should be carefully sought. In most cases, the pleural fluid responds to treatment of the primary disease, whereas resistant or relapsing cases may necessitate pleurodesis.

The prognosis and optimal therapy of patients with pulmonary embolism (PE) are strongly influenced by the presence or absence of associated hemodynamic derangements. Patients with normal systemic arterial pressure have a relatively low risk of recurrent PE and death when treated promptly with therapeutic anticoagulation. Those who present with hypotension, shock, or cardiac arrest, however, have a much higher mortality rate and often receive thrombolytic therapy. Recent evidence indicates that the presence of right ventricular (RV) dysfunction identifies a subgroup of normotensive patients with a much more guarded prognosis who may benefit from more intensive therapy with thrombolytic agents. This article reviews our current understanding of the pathophysiology and diagnosis of RV dysfunction and its impact on the prognosis and therapy of normotensive patients with PE.

To review the Early Lung Cancer Action Project experience and the medical literature from 1993 to 2003 on detection of the small, noncalcified pulmonary nodule by CT in order to formulate a management algorithm for these nodules.

All patients with asthma are at risk of having exacerbations. Hospitalizations and emergency department (ED) visits account for a large proportion of the health-care cost burden of asthma, and avoidance or proper management of acute asthma (AA) episodes represent an area with the potential for large reductions in health-care costs. The severity of exacerbations may range from mild to life threatening, and mortality is most often associated with failure to appreciate the severity of the exacerbation, resulting in inadequate emergency treatment and delay in referring to hospital. This review describes the epidemiology, costs, pathophysiology, mortality, and management of adult AA in the ED and in the ICU.

The use of troleandomycin as adjunctive therapy for the treatment of patients with corticosteroid-dependent asthma first suggested an immunomodulatory effect of the macrolide antibiotics. This led to studies of the macrolides in other chronic airway diseases, such as diffuse panbronchiolitis (DPB), a disease occurring primarily in East Asia. The use of macrolides for the therapy of patients with DPB has led to dramatic improvements in pulmonary function and prolonged survival. Similar benefits have been documented in Japanese studies of bronchiectasis, chronic bronchitis, and sinobronchial syndrome. Clinical and pathologic similarities between DPB and cystic fibrosis (CF) led to the investigation of macrolides for the treatment of CF. Data now suggest that persons with CF will benefit from macrolide therapy. In vitro and in vivo studies suggest that macrolides may inhibit the pulmonary influx of neutrophils, inhibit the release of proinflammatory cytokines, protect the epithelium from bioactive phospholipids, and improve the transportability of airway secretions. The immunomodulatory effects of the macrolides also may be beneficial for the treatment of other chronic inflammatory conditions.

Biofilm-forming bacteria such as Staphylococcus, Haemophilus, and Pseudomonas species resist phagocytosis by host immune cells and the actions of antimicrobial agents. In susceptible individuals, such as patients with cystic fibrosis (CF) or diffuse panbronchiolitis (DPB), strains of Pseudomonas aeruginosa produce a number of virulence determinants that permit colonization and infection of the respiratory tract. P aeruginosa strains isolated from CF and DPB patients typically have a mucoid colony morphology. This is due to the overproduction of alginate, an exopolysaccharide capsule that is composed of D-mannuronic and L-guluronic acids. In addition, the P aeruginosa type IV pilus mediates cell surface translocation by a process known as twitching motility. Both alginate production and twitching motility contribute to the virulence of P aeruginosa, as does the formation of biofilms. Biofilms bind cells and organic and inorganic materials to each other, and to a variety of substrata. Their tightly formed structure reduces antimicrobial activity, promotes bacterial adhesion to lung epithelia, and prevents bacterial dehydration. Prior work has suggested that macrolides have therapeutic value in patients with DPB and CF. We hypothesized that the improved clinical status of these patients was due, in part, to macrolides inhibiting the production of P aeruginosa virulence determinants. Traditionally, macrolides have not been considered to exhibit antipseudomonal activity, as their mean inhibitory concentration (MIC) values for clinical and environmental strains of the microbe range from 50 to 550 microg/mL. In this study, we found that sub-MIC levels of clarithromycin substantially inhibited twitching motility. In addition, the incubation of biofilm-grown P aeruginosa with clarithromycin altered the structure and architecture of the biofilm. Investigating the potential nonribosomal effects of macrolides on opportunistic pathogens such as P aeruginosa and elucidating the molecular mechanisms that underlie the inhibition of twitching motility may lead to more effective treatments of pulmonary infections in patients with CF and DPB.

In addition to their well-known antimicrobial activity, macrolides possess immunomodulatory properties that may confer beneficial effects to patients with respiratory diseases associated with chronic inflammation. These properties include attenuation of inflammatory responses in the lung, mucoregulatory properties, and effects on bronchial responsiveness. Macrolides increase mucociliary clearance, improve sinusitis symptoms, and decrease nasal secretions and polyp size in patients with sinusitis. They also have been shown to modify the inflammatory response associated with chronic sinusitis. In patients with asthma, macrolides have been reported to reduce airway hyperresponsiveness and improve pulmonary function, and have historically been selected for their "steroid-sparing" effect. Preliminary data from studies of patients with COPD have shown improvements in symptom scores and FEV(1) after macrolide treatment. As biological response modifiers, macrolides have the potential to improve the outcomes of patients with inflammatory airway diseases. Large scale, placebo-controlled clinical trials designed to assess long-term efficacy and safety in these diseases are warranted.

Bronchial epithelial damage and mucus hypersecretion are characteristic features of chronic airway inflammation that can impair mucociliary clearance and can cause recurrent or persistent respiratory infection. In response to chemoattractants produced by damaged or inflamed tissue, neutrophils move through sequential steps of recruitment, migration, accumulation, and adhesion to endothelial and bronchial epithelial cells. Neutrophils engage in bacteriocidal activity by phagocytosis, release of lysosomal enzymes, and generation of reactive oxygen species, and they synthesize and release proinflammatory cytokines. Data confirm that many macrolide antibiotics have nonbactericidal properties that include inhibiting inflammatory cell chemotaxis, cytokine synthesis, adhesion molecule expression, and reactive oxygen species production. Macrolides also can decrease airway mucus hypersecretion in patients with diffuse panbronchiolitis, chronic sinusitis, and chronic bronchitis. Macrolides accumulate in neutrophils and macrophages at significantly higher concentrations than in extracellular fluid. This article discusses the action of macrolides on neutrophil accumulation, immune complex-mediated production of nitric oxide, mucin production, and the expanded therapeutic role of macrolides as biological response modifiers.

We describe a case of pulmonary epithelioid hemangioendothelioma, previously known as intravascular bronchoalveolar tumor, in a 35-year-old woman with an initial diagnosis made by transbronchial biopsy. This is a rare disease, with approximately 50 cases described in the literature. All previous cases have been diagnosed by surgical lung biopsy. Although our patient underwent thoracoscopic lung biopsy, the diagnosis was initially made on transbronchial biopsy; to our knowledge, this has not been previously described in the English-language literature. We also described findings on high-resolution CT, both typical and atypical relative to previously published reports. This tumor can affect multiple organs. The prognosis is very unpredictable, with life expectancy ranging from 1 to 15 years. There is no single effective treatment, though spontaneous regression and response to chemotherapy and interferon are reported.

Lung volume reduction surgery (LVRS) has been shown to improve pulmonary function, exercise capacity, quality of life, and survival in selected patients with heterogeneous emphysema. However, LVRS is a major surgical procedure with potential morbidity and mortality. Minimally invasive techniques are emerging to achieve lung volume reduction without open thoracotomy. Devices and techniques under study include one-way bronchial valves inserted via fiberoptic bronchoscopy to promote atelectasis in emphysematous lung, promotion of focal atelectasis and fibrosis by bronchoscopic injection of polymers into emphysematous regions of lung, bronchopulmonary fenestrations to enhance expiratory flow, and thoracoscopic plication or compression of emphysematous lung. The goal of all of these procedures is to replicate the benefit of LVRS without the trauma, risks, and extended recovery of open LVRS. Refinement and application of these techniques will allow patients with emphysema and their physicians and surgeons to choose from a number of viable options for lung volume reduction.

Transforming growth factor (TGF) beta plays an important role in normal pulmonary morphogenesis and function and in the pathogenesis of lung disease. The effect of TGFbeta is regulated via a selective pathway of TGFbeta synthesis and signaling that involves activation of latent TGFbeta, specific TGFbeta receptors, and intracellular signaling via Smad molecules. All three isoforms of TGFbeta are expressed at high levels during normal lung development, being particularly important for branching morphogenesis and epithelial cell differentiation with maturation of surfactant synthesis. Small amounts of TGFbeta are still present in the adult lung, and TGFbeta is involved in normal tissue repair following lung injury. However, in a variety of forms of pulmonary pathology, the expression of TGFbeta is increased. These include chronic lung disease of prematurity as well as several forms of acute and chronic adult lung disease. While TGFbeta1 appears to be the predominant isoform involved, elevated levels of all three isoforms have been demonstrated. The increase in TGFbeta precedes abnormalities in lung function and detectable lung pathology, but correlates with the severity of the disease. TGFbeta plays a key role in mediating fibrotic tissue remodeling by increasing the production and decreasing the degradation of connective tissue via several mechanisms.

Rated number one in overall health system performance by the World Health Organization, the French spend less than half the amount on annual health care per capita that the United States spends. One contributing factor may be the attention given to chronic care. Since the mid-1900s, the French have developed regional community-based specialty systems for patients with chronic respiratory insufficiency or failure. COPD is the major cause of respiratory failure, the fourth leading cause of death in the United States, and its prevalence is increasing. Despite the clinical success of home mechanical ventilation and the potential for cost savings, providing such services in the United States remains a challenge. Lessons from France can inform the development of cost-effective chronic care models in the United States In this article, we review the French experience in the context of the United States Supreme Court's Olmstead decision, mandating that people in "more restrictive settings" such as nursing homes be offered community-based supports. We suggest that regional demonstration projects for patients with chronic respiratory failure or insufficiency can provide an important step in the development of effective chronic care systems in the United States

To evaluate the role of nebulized opioids in COPD.

Respiratory sinus arrhythmia (RSA) is heart rate variability in synchrony with respiration, by which the R-R interval on an ECG is shortened during inspiration and prolonged during expiration. Although RSA has been used as an index of cardiac vagal function, it is also a physiologic phenomenon reflecting respiratory-circulatory interactions universally observed among vertebrates. Previous studies have shown that the efficiency of pulmonary gas exchange is improved by RSA, suggesting that RSA may play an active physiologic role. The matched timing of alveolar ventilation and its perfusion with RSA within each respiratory cycle could save energy expenditure by suppressing unnecessary heartbeats during expiration and ineffective ventilation during the ebb of perfusion. Furthermore, evidence has accumulated of a possible dissociation between RSA and vagal control of that heart rate, suggesting differential controls between the respiratory modulation of cardiac vagal outflow and cardiac vagal tone. RSA or heart rate variability in synchrony with respiration is a biological phenomenon, which may have a positive influence on gas exchange at the level of the lung via efficient ventilation/perfusion matching.

Determining whether a patient's symptoms are the result of heart or lung disease requires an understanding of the influence of pulmonary venous hypertension on lung function. Herein, we describe the effects of acute and chronic elevations of pulmonary venous pressure on the mechanical and gas-exchanging properties of the lung. The mechanisms responsible for various symptoms of congestive heart failure are described, and the significance of sleep-disordered breathing in patients with heart disease is considered. While the initial clinical evaluation of patients with dyspnea is imprecise, measurement of B-type natriuretic peptide levels may prove useful in this setting.