Hereditary thrombophilia and venous thromboembolism.

The hereditary thrombophilias are a group of inherited conditions that predispose to thrombosis. Heritable deficiencies of the endogenous anticoagulants protein C, protein S, and antithrombin have been recognized for some years, but their prevalence, even among patients with familial thrombosis, is low. The recent discoveries of two relatively common thrombophilias, resistance to activated protein C associated with an abnormal factor V gene (factor V Leiden), and prothrombin gene variant 20210A, have substantially increased the likelihood of identifying a heritable predisposing factor in patients with thromboembolism. Modestly elevated levels of plasma homocysteine, which are in part genetically determined, have also recently been associated with an increased risk for venous thromboembolism. A predisposition to thrombosis can now be identified in a substantial minority of patients with venous thromboembolism, and in the majority of patients with familial thrombosis, and there is accumulating evidence that multiple coexisting defects are present in persons with the most marked tendency to thrombosis. The most common causes of hereditary thrombophilia are reviewed with an emphasis on resistance to activated protein C, prothrombin variant 20210A, and hyperhomocystinemia, and the current status of laboratory testing for thrombophilia is discussed.

Pulmonary manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects young women. The respiratory system is more commonly involved in SLE than in any other collagen vascular disease. SLE may affect virtually all components of the respiratory system, including the upper airway, lung parenchyma, pulmonary vasculature, pleura, and respiratory muscles. Respiratory system involvement ranges from symptomatic to fulminant and life threatening. This article reviews the pulmonary manifestations of SLE, including drug-induced SLE.

Pulmonary manifestations of Sjögren's syndrome.

Sjögren's syndrome is one of the most common systemic rheumatic diseases. Pulmonary disease is prevalent in Sjögren's syndrome; respiratory manifestations include chronic cough, obstructive airways disease, pulmonary lymphoma, and interstitial lung disease that may progress to severe pulmonary fibrosis.

Cytomegalovirus as a primary pulmonary pathogen in AIDS.

In patients with AIDS, isolation of cytomegalovirus (CMV) from respiratory secretions is common. It is often found with other pathogens, which has led to debate regarding its role as a primary pulmonary pathogen. A retrospective investigation of patients with AIDS and CMV as a sole pulmonary isolate was performed in an attempt to describe their clinical presentation and course. All patients admitted to the hospital with pneumonia and with BAL or transbronchial biopsy (TBB) specimen positive for CMV between 1991 and 1994 were identified through a review of inpatient records. Inclusion criteria included positive CMV cultures from BAL, cytomegalic inclusion bodies from BAL or TBB, and thorough documentation of the absence of other pulmonary pathogens. Nine patients met the inclusion criteria for CMV pneumonitis. Seven were male and two were female, ages 26 to 44 years, and all had a history of opportunistic infections. Typical clinical presentation was characterized by increased respiratory rate, hypoxemia, and diffuse interstitial infiltrates. The mean CD4 count was 29.6 (+/- 22) cells per cubic millimeter, mean lactate dehydrogenase level was 414 (+/- 301) IU/L, and in seven patients in whom CMV antigen was measured it was greater than 50 positive cells per 200,000 WBCs. Three untreated patients died of respiratory failure and three had autopsy confirmation of CMV pneumonia. Five patients were treated with anti-CMV therapy for at least 2 weeks, and all demonstrated improvement in symptoms, oxygen saturation, and chest radiograph. At 3 months follow-up, all five patients were asymptomatic with no pulmonary symptoms. At 6 months follow-up, three of the five patients remained asymptomatic; the other two died of other opportunistic infections. In at least these nine patients, CMV represented a primary pulmonary pathogen. Patients who were treated responded quickly and were able to be discharged home from the hospital with marked improvement in their symptoms. We recommend that clinicians consider this diagnosis in the proper setting and consider treatment with anti-CMV therapy.

Current diagnostic methods and medical management of thoracic empyemas.

Infections can invade the normally sterile pleural space leading to the development of parapneumonia effusions or empyemas. Pneumonia, thoracic surgery, and trauma, together, are responsible for most cases of empyemas. Pneumococci and staphylococci remain the predominant etiologic organisms. In addition, gram-negative aerobic bacteria and anaerobes are emerging as important pathogens. Most parapneumonic pleural effusions, regardless of their underlying etiology and bacteriology, evolve through definable stages. For each stage of the disease, specific therapeutic measures, either medical or surgical, are available.

Use of neodymium yttrium aluminum garnet laser in long-term palliation of airway obstruction.

Palliation of acute airway obstruction using the neodymium yttrium aluminum garnet (Nd-YAG) laser was studied in 54 patients who presented over a 42-month period to the Yale cardiothoracic surgery service. Thirty-seven patients had bronchogenic carcinoma; 27 had stage IIIB or IV disease. Nine patients had endobronchial metastases from a primary nonbronchogenic carcinoma. Eight patients had benign disease. A total of 109 Nd-YAG laser tumor ablations were performed. In addition, 32 patients underwent postoperative brachytherapy. Median survival for all patients was 12 months. Patients with bronchogenic carcinoma had a median survival of five months. Fifteen of 20 patients (75%) alive at the time of follow-up reported continued palliation as shown by an improved postoperative Karnofsky score. There was no survival benefit from Nd-YAG laser ablation of endobronchial bronchogenic carcinoma; however, the Nd-YAG laser provided good to excellent palliation in the majority of patients on long-term follow-up.

Burns and smoke inhalation.

Smoke inhalation injury affects nearly one third of all major burn victims. Significant inhalation exposures must be suspected in persons who were entrapped in a closed space or who became unconscious during a fire. Each individual fire generates a characteristic smoke depending on the type of materials burnt, temperatures reached during pyrolysis, and the availability of oxygen to sustain combustion. In addition to variable amounts of thermal loads, firesmoke may contain mixtures of carbon monoxide, hydrogen cyanide, nitrogen oxides, and other highly irritating gases. Each constituent of firesmoke may potentially create pulmonary and systemic toxicities and must be considered in every victim of smoke inhalation.

Lung cancer in the elderly patient.

One half of all cases of lung cancer occur in patients aged 65 years and older. Although adenocarcinoma is the predominant histologic subtype in the general population, squamous cell carcinoma has remained the most common type in the elderly. Although lung cancer tends to present at a less advanced stage with increasing age, the percentage of elderly patients undergoing treatment tends to decline despite the fact that they can tolerate the aggressive therapy that may enhance survival.

The role of bronchoscopy in lung cancer.

Flexible fiberoptic bronchoscopy is the most useful invasive technique for diagnosing lung cancer. This article details the use and efficacy of bronchoscopy with such established techniques as forceps biopsy, brush biopsy, and bronchial washing in the diagnosis and staging of bronchoscopically visible central lung cancer and peripheral lung cancer. The efficacy of such newer techniques as transbronchial needle aspiration, transbronchial curettage, ultrathin fiberoptic bronchoscopy, and quantitation of tumor markers in bronchoalveolar lavage fluid is also discussed, along with the complications of bronchoscopy and new techniques for detecting early lung cancer.

Cardiovascular manifestations of connective tissue disorders.

Disease processes that involve abnormalities of the connective tissue are protean in their manifestations because of the ubiquitous and crucial function that connective tissue serves in the body. Connective tissue supports of the heart and vascular structures play an integral role in normal cardiovascular performance, and it is not surprising that many connective tissue disorders produce important pathophysiologic processes that affect cardiac and vascular elements. The article focuses on the cardiac and vascular manifestations of hereditary and acquired forms of connective tissue disease. Special attention is focused on the use of imaging modalities and their role in diagnosing cardiovascular pathology produced by collagen disorders.

Cardiac evaluation.

Over the past decade there has been a dramatic, rapid development of new imaging modalities used in the evaluation of the cardiac patient. These newer techniques are frequently complex and specialized in their application and interpretation. Nonetheless, the prevalence of cardiac disease in the United States, and the wide application of these diagnostic tests, mandate that the well-rounded clinician has a basic understanding of the utility of these diagnostic modalities. Unfortunately, the burgeoning field of cardiac imaging seems at times to overshadow our most important basic diagnostic tools, namely, the history, physical exam, chest radiograph, and electrocardiogram (ECG). This review will attempt to impart a basic understanding of the newer cardiac diagnostic tests and their utility in various disease states. Emphasis on the importance of the basic clinical exam and the precise integration of specific diagnostic tests into the cardiac evaluation will be emphasized. The article will deliver a basic review of exercise treadmill testing, echocardiography, radionuclide imaging techniques, magnetic resonance imaging, and cardiac catheterization. It is hoped that this review will impart to the noncardiologist clinician a basic understanding of the cardiovascular diagnostic techniques so that an accurate, precise, cost-effective, efficient diagnostic plan for the patient with cardiovascular disease can be developed and applied.

Right ventricular function at rest and during exercise in chronic obstructive pulmonary disease.

Right ventricular ejection fraction (RVEF), a measure of systolic pump performance of the right ventricle, is frequently depressed at rest or during exercise in patients with chronic obstructive pulmonary disease (COPD). The most common cause of reduced RVEF in COPD is augmentation of right ventricular afterload, namely an increase in pulmonary artery pressure and pulmonary vascular resistance. Therapy with agents that decrease the afterload on the right ventricle have the potential to improve the systolic performance of this chamber. Oxygen, vasodilators such as hydralazine and nifedipine, theophylline, and sympathomimetics all may augment RVEF in part by reducing pulmonary vascular resistance and, in some cases, pulmonary artery pressures in patients with COPD and cor pulmonale. However, only oxygen therapy has been shown to improve survival.

Pulmonary manifestations of systemic lupus erythematosus.

The respiratory system is affected more commonly in systemic lupus erythematosus (SLE) than in any other collagen vascular disease. In this article the many different manifestations of SLE in the pleura, lung parenchyma, lung vasculature, upper and lower airways, and respiratory muscles are reviewed. Moreover, indirect involvement of the respiratory system with SLE is discussed with special reference to pulmonary infection and drug-induced SLE pulmonary disease.

Pulmonary manifestations of scleroderma.

Scleroderma is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities. The lungs are commonly involved in scleroderma, ranking only behind the skin, the peripheral vasculature, and the esophagus in frequency of organ involvement. Respiratory symptoms are, in a very few cases, the presenting manifestation of the disease. Abnormalities of pulmonary function in affected patients include a restrictive ventilatory defect, air flow obstruction, and a depressed diffusing capacity for carbon monoxide, which may be an isolated early finding. Interstitial lung disease and honeycombed lung are the most common pulmonary parenchymal abnormalities seen on chest radiographs. Enlargement of the cardiac silhouette and pulmonary artery due to scleroderma-induced pulmonary vascular disease is also noted. High-resolution computed tomography (HRCT) apparently is a sensitive, potentially useful technique for detecting occult interstitial lung disease in patients with scleroderma. Bronchoalveolar lavage usually shows an increase in total cell count and in the percentage of granulocytes; occasionally, there is a predominantly mononuclear (lymphocytic) cell alveolitis. Premortem and postmortem studies reveal two predominant lung lesions: (1) interstitial lung disease and (2) pulmonary vascular disease. Pulmonary vascular disease may occur in the absence of interstitial lung disease, particularly in patients with limited, as opposed to diffuse, scleroderma. The overall mortality rate in scleroderma is 50% at 7 years, and pulmonary complications are the major cause of death. No prospective, well-controlled studies have established that treatment alters the natural course of pulmonary disease in patients with scleroderma. Both D-penicillamine and cyclophosphamide have shown promise for treating patients with interstitial lung disease, and nifedipine may be useful for treating patients with early pulmonary vascular disease.

The right ventricle in pulmonary disease.

Abnormal pulmonary function that causes pulmonary artery hypertension increases right ventricular work. To compensate, the right ventricle enlarges, and cor pulmonale develops. Right ventricular failure occurs when these adaptive mechanisms cannot compensate for the hemodynamic burden. The various pulmonary diseases that are associated with right ventricular overload and the physiologic responses of the right ventricle to increased afterload are discussed in this article.

Mechanical heart-lung interaction in the adult respiratory distress syndrome.

We have discussed the complex hemodynamic changes that occur throughout the respiratory cycle during spontaneous and mechanical ventilation. In patients, many cumulative factors account for the total hemodynamic burden of inspiration and expiration. Thus, the change in pleural pressure, ventilation rate, mode of ventilation, amount of spontaneous ventilation, underlying lung and cardiac disease, and intravascular volume status all affect cardiocirculatory equilibrium. In addition, in the patient with ARDS, various immune mediators that are released into the circulation will affect LV function. Knowledge of the effects discussed in this article will aid the physician in choosing therapeutic options for patients with ARDS.

Cor pulmonale in chronic obstructive pulmonary disease. Circulatory pathophysiology and management.

The development of pulmonary hypertension and right ventricular failure in COPD patients signals a poor prognosis. In hypoxic patients, long-term oxygen therapy prolongs life and appears to prevent or lessen the progression of pulmonary hypertension. However, oxygen therapy does not benefit and is not indicated for all COPD patients, and even in those patients who improve with oxygen, there remains a need to further improve survival. Therefore, there continues to be active investigations into pharmacologic agents that might reduce pulmonary hypertension or improve right ventricular function. Although many agents appear to have salutary acute effects, it has been more difficult to establish evidence for sustained hemodynamic benefits from chronic drug therapy. Furthermore, some effective agents may not provide additive benefit when combined with standard supplemental oxygen use, although the available data are limited. Clearly, further research is necessary to identify which COPD patients, if any, may benefit from either beta-agonists or vasodilators for the treatment or prevention of cor pulmonale at some time during the natural history of their disease.

Imaging techniques for assessing pulmonary artery hypertension and right ventricular performance with special reference to COPD.

Several imaging techniques, both noninvasive and minimally invasive, have now been applied widely for determining cardiovascular performance in patients with chronic respiratory disease, particularly COPD. Moreover, some of these techniques are useful for evaluating response to therapeutic intervention in these patients. The plain chest radiograph is useful primarily for detecting the presence of pulmonary artery hypertension in patients with COPD. Radionuclide angiocardiography, using either first-pass techniques or the gated equilibrium technique, is particularly useful for determining right and left ventricular ejection fraction. Echocardiography has evolved as a technique for assessing right ventricular size and function and, in some cases, the degree of pulmonary artery hypertension.