Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance. These diseases include chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung disease, pneumonia, and alveolar proteinosis. Understanding of the mechanisms that disturb the lung surfactant system may lead to novel rational therapies for these diseases.

Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs). Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

Pulmonary surfactant is a unique mixture of lipids and surfactant-specific proteins that covers the entire alveolar surface of the lungs. Surfactant is not restricted to the alveolar compartment; it also reaches terminal conducting airways and is present in upper airway secretions. While the role of surfactant in the alveolar compartment has been intensively elucidated both in health and disease states, the possible role of surfactant in the airways requires further research. This review summarizes the current knowledge on surfactant functions regarding the airway compartment and highlights the impact of various surfactant components on allergic inflammation in asthma.

Background: Various estimates of the incidence and mortality rate of the acute (adult) respiratory distress syndrome (ARDS) have been published. The studies that led to those estimates were based on relatively small patient populations and employed variable diagnostic identifiers of ARDS. The purpose of this study was to estimate the incidence of ARDS and its mortality rate from a large database to which refined diagnostic criteria were applied. We conducted a retrospective review of all hospital discharges over a 4-year period, using screening criteria designed to select patients with ARDS. Discharges from all acute care hospitals in the state of Maryland were reviewed using a computer database from the Health Services Cost Review Commission (HSCRC). Patients ≥ 12 years of age were included. Screening criteria consisted of ICD-9 codes 518.5 and 518.82 cross-referenced with procedural codes for ventilatory support (96.70, 96.71 and 96.72). Data were normalized to the number of cases per 100,000 people. Results: During the 4-year study period there were 2,501,147 hospitalizations. Applying the ICD-9 ARDS criteria yielded lower and upper limits of 159-205, 439-568, 531-694 and 529-720 cases of ARDS for 1992, 1993, 1994 and 1995, respectively. Normalizing for a population of 5 million yields yearly lower and upper limit rates of 3.2-4.2, 8.8-11.4, 10.6-13.8 and 10.5-14.2 cases of ARDS per 100,000 people. Mortality upper and lower limit rates based upon the same duration, admissions and population were 38-49%, 39-52%, 36-47%, and 36-49%, respectively. Conclusions: The incidence of ARDS in Maryland is in the range of 10-14 cases per 100,000 people. The ARDS mortality rate is 36% to 52%, similar to that calculated in previous studies.

Background The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS). Methods Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM. Results The pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage. Conclusions Postmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury.

Intra-abdominal hypertension (IAH) associated with organ dysfunction defines the abdominal compartment syndrome (ACS). Elevated intra-abdominal pressure (IAP) adversely impacts pulmonary, cardiovascular, renal, splanchnic, musculoskeletal/integumentary, and central nervous system physiology. The combination of IAH and disordered physiology results in a clinical syndrome with significant morbidity and mortality. The onset of the ACS requires prompt recognition and appropriately timed and staged intervention in order to optimize outcome. The history, pathophysiology, clinical presentation, and management of this disorder is outlined.

Background The purpose of the present study is to determine whether airway pressure release ventilation (APRV) can safely enhance hemodynamics in patients with acute lung injury (ALI) and/or adult respiratory distress syndrome (ARDS), relative to pressure control ventilation (PCV). Method Patients with severe acute lung injury or ARDS who were managed with inverse-ratio pressure control ventilation, neuromuscular blockade and a pulmonary artery catheter were switched to APRV. Hemodynamic performance, as well as pressor and sedative needs, was assessed after discontinuing neuromuscular blockade Results Mean age was 58 ± 9 years (n = 12) and mean Lung Injury Score was 7.6 ± 2.1. Temperature and arterial oxygen tension/fractional inspired oxygen (FiO2) were similar among the patients. Peak airway pressures fell from 38 ± 3 for PCV to 25 ± 3 cmH2O for APRV, and mean pressures fell from 18 ± 3 for PCV to 12 ± 2 cmH2O for APRV. Paralytic use and sedative use were significantly lower with APRV than with PCV. Pressor use decreased substantially with ARPV. Lactate levels remained normal, but decreased on APRV. Cardiac index rose from 3.2 ± 0.4 for PCV to 4.6 ± 0.3 l/min per m2 body surface area (BSA) for APRV, whereas oxygen delivery increased from 997 ± 108 for PCV to 1409 ± 146 ml/min for APRV, and central venous pressure declined from 18 ± 4 for PCV to 12 ± 4 cmH2O for APRV. Urine output increased from 0.83 ± 0.1 for PCV to 0.96 ± 0.12 ml/kg per hour for APRV. Conclusion APRV may be used safely in patients with ALI/ARDS, and decreases the need for paralysis and sedation as compared with PCV-inverse ratio ventilation (IRV). APRV increases cardiac performance, with decreased pressor use and decreased airway pressure, in patients with ALI/ARDS.

In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD) with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo®) to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion) also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase) were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

According to the Frank-Starling relationship, a patient is a 'responder' to volume expansion only if both ventricles are preload dependent. Mechanical ventilation induces cyclic changes in left ventricular (LV) stroke volume, which are mainly related to the expiratory decrease in LV preload due to the inspiratory decrease in right ventricular (RV) filling and ejection. In the present review, we detail the mechanisms by which mechanical ventilation should result in greater cyclic changes in LV stroke volume when both ventricles are 'preload dependent'. We also address recent clinical data demonstrating that respiratory changes in arterial pulse (or systolic) pressure and in Doppler aortic velocity (as surrogates of respiratory changes in LV stroke volume) can be used to detect biventricular preload dependence, and hence fluid responsiveness in critically ill patients.