Current Respiratory Medicine Reviews - Volume 3, Issue 3, 2007

Determining the volume status in critically ill patients is sometimes challenging. This is particularly difficult among those patients with a pre-existing history of congestive heart failure (CHF) and a new systemic and catastrophic illness (i.e., severe sepsis). In critically ill patients, interstitial lung edema is the hallmark of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [1]. A quantitative measurement of lung edema in these patients could provide a useful marker of disease severity and progression. Techniques aimed at determining extravascular lung water (EVLW) may be derived from a variety of methods such as blood ultrasound velocity changes following injections of 0.9% and 5% saline [2]. Bioimpedance spectroscopy can measure total body water (TBW) and its intracellular fluid (ICF) and extracellular fluid (ECF) compartments. The indicator dilution methods and quantitative computed tomography (CT), however, are among the most commonly used techniques, both clinically and experimentally to quantify lung edema. In this issue of Current Respiratory Medicine Reviews, Sakka presents a comprehensive review on the techniques and utility of measurement of EVLW in critically ill patients. This review provides readers with general principles of the techniques utilized and, in particular, the usefulness of the single transpulmonary thermodilution technique [3]. This method has gained popularity over the past decade. As indicated by Sakka, the assessment of EVLW using other methods such as chest radiography and arterial blood gases is very imprecise [3]. In addition, these methods prove difficult to quantify the extent of clinically relevant pulmonary edema [4]. The single transpulmonary thermal indicator technique appears to have multiple potential advantages, including detection of incipient pulmonary edema and monitor response to management. The bigger question remains: Is there any clinical utility of the EVLW measurements? Some studies have demonstrated a direct correlation between the level of EVLW and mortality [5]. Moreover, EVLW measurement could potentially help the clinician characterize better patients with ARDS. Guiding fluid therapy in these patients is commonly quite difficult. Therefore, techniques such as thermo dilution methods and treatment algorithms for fluid replacement would decrease the duration of mechanical ventilation and length of stay in the intensive care unit in patients with ALI and ARDS [2]. The reader, however, must be careful when evaluating EVLW measurements in daily clinical practice. Scientists propose theories and assess those theories in the light of observational and experimental evidence; what distinguishes science from voodoo is the careful and systematic way in which hypothesis are critically evaluated based on the available evidence. Until recently, it was considered sufficient to understand disease processes in order to prescribe a drug or other form of treatment. However, when these treatment modalities were subjected to randomized, controlled clinical trials (RCTs) examining clinical outcomes and not physiological processes, the outcome was not always favorable. The RCT has become the reference in medicine by which to judge the effect of an intervention on patient outcome, because it provides the greatest justification for conclusion of causality is subject to the least bias, and provides the most valid data on which to base all measures of the benefits and risk of particular therapies. For EVLW measurements to “take off” in clinical critical care medicine, a large RCT with thousands of patients must be conducted and prove that not only these measurements provide useful information, but that also allow the clinician to tailor the management of these critically ill patients to improve survival and length of stay. REFERENCES [1] Lechin AE, Varon J. Adult respiratory distress syndrome (ARDS): The basics. J Emerg Med 1994; 12(1): 63-8. [2] Michard F. Beside assessment of extravascular lung water by dilution methods: temptations and pitfalls. Crit Care Med 2007; 35(4): 1186-92. [3] Sakka SG. Measurement of extravascular lung water in critically ill patients. Curr Respir Med Rev 2007; 2007; 3(3): 206-213.

High-resolution computed tomography (CT) of the lung is a powerful diagnostic tool in revealing morphological abnormalities that closely correspond to those of the pathological tissue specimen. High-resolution CT is usually obtained at the end of deep inspiration; however, additional CT obtained at the end of deep exhalation (expiratory CT) provides a different set of information. The lung usually shows a homogeneous increase in lung density after forced exhalation, and the cross-sectional area decreases accordingly in healthy subjects; however, those areas peripheral to diseased airways often show no increase in lung density or decrease in cross-sectional area after exhalation. These areas (airtrapping areas) are seen in various diffuse lung diseases, including small airway diseases, some interstitial lung diseases, and even in normal subjects. Irrespective of the disease or condition, the extent of air-trapping approximately correlates with obstructive functional impairment. In patients with suspected lung parenchymal disease, air-trapping can be the only imaging abnormality; thus, expiratory CT can visualize early or mild parenchymal lung disease before the development of overt abnormalities. In this manuscript, the various techniques of paired inspiratory and expiratory high-resolution CT are reviewed and the normal appearances of expiratory images are described. Correlation of imaging findings with pulmonary function tests is discussed and the clinical impact of the technique is reviewed for some of the diffuse parenchymal lung diseases.

Heart Failure (HF) is a significant health care concern with in both the United States and Europe. While there are a number of mechanisms that lead to HF, a decline in the response to exercise is common amongst the various etiologies. Cardiopulmonary exercise testing (CPET) is a well established diagnostic and prognostic tool in the HF population. This exercise testing technique allows for the measurement of oxygen consumption (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) across time. Cardiovascular and skeletal muscle dysfunction is considered central to the often abnormal exercise response observed in the HF population. As such, VO2 at peak exercise is the most recognized CPET variable in patients with HF. In recent years, however, the importance of assessing VE during exercise, either alone or in combination with expired gases, has been highlighted in a number of investigations. The VE-VCO2 relationship, exercise periodic breathing (EPB) and the oxygen uptake efficiency slope (OUES) are, to this point, the most studied CPET measurements incorporating VE in the HF population. Of these, the VE-VCO2 relationship has received the greatest amount of attention. This review will address the clinical significance of these CPET measurements in the HF population.

Idiopathic pulmonary fibrosis (IPF) is a disease with limited therapeutic options. Corticosteroids and immunouppressive agents have been the mainstays of treatment, primarily due to their anti-inflammatory properties. However, they have demonstrated minimal efficacy and significant toxicity. Recent efforts have sought to target other aspects of the pathophysiology of this condition. Several investigators have hypothesized that imbalances of coagulation and fibrinolysis play a role in the pathophysiology of IPF. Thrombin has been identified as a possible trigger of fibroblast proliferation in IPF, suggesting a role for thrombin inhibition in modifying the course of disease. Furthermore, anticoagulation may have a role in preventing thrombotic complications in IPF patients with secondary pulmonary hypertension. This review will discuss the potential role for anticoagulation in the treatment of IPF. One randomised control trial has demonstrated a significant survival benefit associated with anticoagulation of IPF patients. We will review the evidence supporting this treatment strategy, as well as its possible mechanisms of action.

Alterations in the composition of the extracellular matrix (ECM) and its abundance are important features of airway fibrosis, which is observed in lung disorders such as asthma, COPD and cystic fibrosis. The ECM was originally thought to only play a passive, structural role by providing a stable framework for the resident airway cells from which they are synthesized. However, there is now increasing evidence that the ECM impacts on the biological activity of smooth muscle cells, fibroblasts, and epithelial cells. Current anti-asthma therapy is only partially effective in preventing matrix deposition in chronic asthma, and does not reverse established fibrosis. Little is known about the signal transduction pathways that mediate ECM effects on airway smooth muscle cells. Importantly, in order for the ECM to influence myocyte phenotype and function, the cell must possess selective receptors (integrins) to induce intracellular signalling pathways. This mini-review explores current knowledge of the role of the ECM and its receptors (integrins) on airway smooth muscle phenotype and function and highlights their possible importance in airway disease. New signalling molecules that may be essential in mediating ECM-integrin interactions will also be discussed as they may prove to be novel targets for developing new therapies for asthma.

In critically ill patients, capillary leakage often occurs which in the lungs may lead to pulmonary edema by increased microvascular pressure and permeability. However, clinical assessment of the extent of pulmonary capillary leakage and pulmonary edema is difficult. Several decades ago, the transpulmonary double indicator (thermo-dye) dilution technique has been introduced for quantification of extravasastion of fluids in the lungs by determination of the extravascular lung water (EVLW). The thermo-dye is based on simultaneous central venous injection of a freely diffusible indicator (‘cold’) and a plasma-bound indicator (indocyanine green). This technique has been extensively validated in animal experiments using post-mortem gravimetry and in humans using radionuclide techniques. However, the thermo-dye dilution technique is relatively expensive and time consuming therefore assessment of EVLW is increasingly performed by single transpulmonary thermodilution, which according to animal experimental and clinical studies is sufficiently accurate for estimation of EVLW. Using EVLW to guide the management of patients with both cardiac and non-cardiac pulmonary edema (ARDS) has been shown to reduce the duration of mechanical ventilation, length of stay in the intensive care unit and potentially intensive care costs. EVLW-guided therapy also reduced mortality in those patients with congestive heart failure and ARDS. Recent clinical studies have shown that in critically ill patients EVLW correlates with the severity of lung injury and that it does have a prognostic value. Thus, monitoring EVLW can be a useful additional tool in the goaldirected therapy of critically ill patients, especially those with severe sepsis and sepsis-induced acute lung injury.

Granuloma, a collection of various inflammatory cells composed of lymphocytes, epithelioid cells, giant cells, mononuclear cells, eosinophils, plasma cells, and fibroblasts is a host response to an antigen(s). Specific patterns of the granulomatous response such as necrosis, caseation, and the presence or absence of microorganisms or foreign bodies aid in securing the diagnosis. The common causes of granulomatous lung disease include sarcoidosis, hypersensitivity pneumonitis, Wegener's granulomatosis, mycobacterial infections, fungal diseases, parasitic infestations, and drugs. This review, designed for practicing pulmonologists, emphasizes diagnosis and treatment of some of the common pulmonary granulomas.

Polymyositis and dermatomyositis (PM-DM) are forms of idiopathic inflammatory myositis. Interstitial lung disease (ILD) in PM-DM is recognized as a serious complication and a major cause of death in this disease. According to the results of immunophenotyping of lymphocytes in bronchoalveolar lavage fluid, cytotoxic T lymphocytes may be major pulmonary inflammatory cells of ILD in PM-DM. Glucocorticoids are considered the first-line drug treatment for PMDM patients with ILD, however they are often not sufficient to obtain improvement of ILD as a single agent. Furthermore, the addition of immunosuppressive drugs becomes necessary as steroid sparing agents to avoid the severe sideeffects often seen with high-dose steroid treatment. Cyclophosphamide, cyclosporin, and tacrolimus were reported to be effective in treatment of refractory ILD in PM-DM. Although other immunosuppressive agents; mycophenolate mofetil, intravenous immunoglobulin, and anti-TNF agents have appeared as promising agents for refractory PM-DM, the efficacy on ILD in PM-DM is still unknown. Even if treatment is initiated early in the course of the disease, some patients still develop irreversible fatal lung fibrosis under aggressive immunosuppressive therapy. The fastest way to find the most effective treatment may be to investigate the pathogenesis of the disease in detail before initiation of immunosuppressive therapy including glucocorticoids.

Chemotherapy-induced respiratory failure is being increasingly recognized as a cause of respiratory failure in the intensive care unit. The frequency of chemotherapy-induced respiratory failure is low, however with increasing number of patients receiving new chemotherapeutic agents more cases can be expected to be seen. Chemotherapy-induced respiratory failure can be due to bronchospasm and hypersensitivity reactions, pulmonary hemorrhage, interstitial pneumonitis, eosinophilic pneumonia, and non-cardiogenic pulmonary edema. Pulmonary and critical care physicians should be aware of the clinical presentation of chemotherapy-induced respiratory failure.

Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases. Severe CAP (SCAP) patients that required ICU admission carry the highest mortality rates. Multiple sets of clinical practice guidelines have been published in the past few years addressing the treatment of CAP, and they all agree that CAP patients admitted to the hospital represent a major concern, and appropriate empiric therapy should be instituted to improve clinical outcomes. The purpose of this article is to review the current literature regarding the optimal empiric selection of antibiotic therapy for patients with SCAP. In addition emphasis on the empiric and direct therapy will be made on patients with bacteremic pneumococcal pneumonia.