We present a review of the English-language literature from 1972 through 2000 pertaining to systemic high BP in patients with sleep-disordered breathing (SDB). We reviewed studies assessing the relationship between obstructive sleep apnea, central sleep apnea or periodic breathing, and systemic high BP, and present an approach to the management of these patients. Complications of obesity and the role of the sympathetic nervous system are reviewed as well. It is the aim of these reviews to draw qualified conclusions, based on the current literature, with regard to SDB as a causative or contributory factor in systemic hypertension.

We present a two-part review of the English-language literature pertaining to drug therapy for systemic high BP in patients with pulmonary diseases. Part I examines the literature pertaining to the use of antihypertensive drugs in patients with systemic hypertension and coexisting pulmonary conditions, especially COPD and asthma. Part II of the series reviews studies assessing the relationship between sleep-disordered breathing (including the role of the sympathetic nervous system) and systemic hypertension, and presents an approach to the management of these patients. It is the aim of both parts of this review to make qualified conclusions and recommendations applying a methodologic critique to assess the current literature. In the first part of this series, we review the demographics of hypertension in patients with COPD. This is followed by an extensive review of the use of specific classes of antihypertensive drug therapies in patients with pulmonary disease. The antihypertensive agents reviewed include diuretics, calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists, beta-adrenergic blocking agents, and alpha-beta-blockers and other non-beta-blocker classes. Additionally, the renin angiotensin system is briefly reviewed, with a discussion of how angiotensin-converting enzyme inhibitors induce cough, especially in pulmonary and congestive heart failure patients.

Spontaneous pneumothorax is a common complication in patients with cystic fibrosis (CF). It is thought to occur more frequently in patients with more advanced disease. Recommendations on the management of pneumothorax in CF are based on retrospective analyses and reports from CF centers. The following is a review of what has been published regarding the incidence and management of pneumothorax in this population, with some comment on the pathogenesis of the complication.

Interferons (IFNs) are a family of cytokine mediators that are critically involved in alerting the cellular immune system to viral infections of host cells. There are three major classes of IFNs, as follows: IFN-alpha; IFN-beta; and IFN-gamma. IFNs are being investigated and applied in various respiratory disorders, including interstitial lung diseases, lung cancer, malignant mesothelioma, malignant pleural effusions, and respiratory infections. Recent promising preliminary results concerning patients with idiopathic pulmonary fibrosis who have been treated with IFN-gamma1b should prompt the performance of further confirmatory well-designed multicenter trials. IFN-gamma is emerging as an important cytokine for use in the treatment of patients with infectious diseases, including multidrug-resistant pulmonary TB. A better understanding of IFN biology, indications, side effect profiles, and toxicity management will aid in optimizing its use in the treatment of patients. The purpose of this article is, therefore, to review the current clinical use of IFNs in the treatment of patients with respiratory diseases.

The management of patients with suspected or known lung cancer is becoming increasingly complex. State-of-the-art care often requires input from many sources, including pulmonology, thoracic surgery, medical oncology, radiation oncology, pathology, and radiology. Valuable contributions to care also come from nursing, social work, psychology, psychiatry, pastoral care, and palliative care, among others. As a result, multidisciplinary input into care is vital. Patients with suspected lung cancer should be expeditiously evaluated and referred for management. Clear and understandable information on the diagnosis, treatment options, and possible outcomes should be provided. Treatment recommendations should be based on locally agreed-on adaptations of clinical practice guidelines. Provisions for ongoing care should be apparent to all concerned

Evidence-based practice guidelines for end-of-life care for patients with lung cancer have been previously available only from the British health-care system. Currently in this setting, there has been increasing concern in attaining control of the physical, psychological, social, and spiritual distress of the patient and family. This American College of Chest Physicians'-sponsored multidisciplinary panel has generated recommendations for improving quality of life after examining the English-language literature for answers to some of the most important questions in end-of-life care. Communication between the doctor, patient, and family is central to the active total care of patients with disease that is not responsive to curative treatment. The advance care directive, which has been slowly evolving and is presently limited in application and often circumstantially ineffective, better protects patient autonomy. The problem-solving capability of the hospital ethics committee has been poorly utilized, often due to a lack of understanding of its composition and function. Cost considerations and a sense of futility have confused caregivers as to the potentially important role of the critical care specialist in this scenario. Symptomatic and supportive care provided in a timely and consistent fashion in the hospice environment, which treats the patient and family at home, has been increasingly used, and at this time is the best model for end-of-life care in the United States.

The majority of patients who acquire lung cancer will have troublesome symptoms at some time during the course of their disease. Some of the symptoms are common to many types of cancers, while others are more often encountered with lung cancer than other primary sites. The most common symptoms are pain, dyspnea, and cough. This document will address the management of these symptoms, and it will also address the palliation of specific problems that are commonly seen in lung cancer: metastases to the brain, spinal cord, and bones; hemoptysis; tracheoesophageal fistula; and obstruction of the superior vena cava.

The following two distinctly different issues should be taken into account when planning patient care following curative-intent therapy for lung cancer: adequate follow-up to manage complications related to the curative-intent therapy; and surveillance to detect recurrences of the primary lung cancer and/or development of a new primary lung cancer early enough to allow potentially curative retreatment. Follow-up for complications should be performed by the specialist responsible for the curative-intent therapy and should last 3 to 6 months. Recurrences of the original lung cancer will be more likely during the first 2 years after curative-intent therapy, but there will be an increased lifelong risk of approximately 1 to 2% per year of developing a metachronous, or new primary, lung cancer. A standard surveillance program for these patients is recommended based on periodic visits, with chest-imaging studies and counseling patients on symptom recognition. Whether subgroups of patients with a higher risk of developing a metachronous lung cancer (eg, those patients whose primary lung cancer was radiographically occult or central and those patients surviving for > 2 years after treatment for small cell lung cancer) should have a more intensive surveillance program is presently unclear. The surveillance program should be coordinated by a multidisciplinary tumor board and overseen by the physician who diagnosed and initiated therapy for the original lung cancer. Smoking cessation is recommended for all patients following curative-intent therapy for lung cancer.

Among patients with lung cancers, the proportion of those with small cell lung cancer (SCLC) has decreased over the last decade. SCLC is staged as limited-stage disease and extensive-stage disease. Standard staging procedures for SCLC include CT scans of the chest and abdomen, bone scan, and CT scan or MRI of the brain. The role for positron emission tomography scanning in the staging of SCLC has yet to be defined. Limited-stage disease is treated with curative intent with chemotherapy and radiation therapy, with approximately 20% of patients achieving a cure. The median survival time for patients with limited-stage disease is approximately 18 months. Extensive-stage disease is treated primarily with chemotherapy, with a high initial response rate of 60 to 70% and a complete response rate of 20 to 30%, but with a median survival time of approximately 9 months. Patients achieving a complete remission should be offered prophylactic cranial irradiation. Currently, there is no role for maintenance treatment or bone marrow transplantation in the treatment of patients with SCLC. Relapsed or refractory SCLC has a uniformly poor prognosis. In this section, evidence-based guidelines for the staging and treatment of SCLC are outlined.

This chapter of the Lung Cancer Guidelines addresses patients with particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLC), and solitary metastases. For patients with a Pancoast tumor, a multimodality approach, involving chemoradiotherapy and surgical resection, appears optimal provided appropriate staging has been carried out. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. When carefully staged and selected, however, such patients appear to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment from what would be dictated by the primary tumor alone. On the other hand, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLC do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and those with a second primary lung cancer, although criteria to distinguish them have not been defined. Finally, some patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit substantially from resection.

Stage IV non-small cell lung cancer (NSCLC) denotes the presence of metastatic disease and is largely incurable using present-day therapies. Chemotherapy remains a therapeutic option in this patient population, and there are many pertinent issues surrounding its use in patients with stage IV NSCLC. Eleven questions were framed by the American College of Chest Physicians Lung Cancer Guidelines Committee, and these were addressed by a systematic search of the available literature. The issues addressed included the identification of prognostic factors in selecting patients for chemotherapy and a critical analysis of the survival benefit provided by chemotherapy. Given the development of several new chemotherapy agents over the past decade, the impact that these agents have made was addressed as well as the definition of a standard of care regarding chemotherapeutic regimens. Given the fact that chemotherapy does not represent a curative option, other issues addressed were the optimal duration of treatment as well as its impact on symptom relief and quality of life, the role of second-line therapy, and the outcomes expectations from both first-line and second-line chemotherapy. The question of what specialty delivered the chemotherapy also was addressed. Once the data were identified, a critical analysis was undertaken attempting to objectively portray the data in support of answers for each of the questions posed. We believe the data support the fact that properly selected patients benefit from chemotherapy with regard to survival and palliation in both first-line and second-line settings. It appears that in trials addressing the duration of first-line therapy, this survival and palliative benefit occurs early, and prolonged therapy is not indicated. Therapy in this setting is cost-effective, and there are several regimens that can be considered to be "standard-of-care" options. Physicians involved in the diagnosis of these patients should be aware of the potential benefits of chemotherapy, allowing them to give recommendations to patients that are based on data derived from clinical trials. In addition, this awareness will allow them to make referrals, when appropriate, to physicians who are trained in the administration of chemotherapy and the management of patients undergoing such therapy.

Stage IIIB includes patients with T4, any N, M0, and any T, N3, M0. Surgery may be indicated only for carefully selected T4N0M0 patients with or without neoadjuvant chemotherapy or chemoradiotherapy. Patients with N3 lymph node involvement are not considered as surgical candidates. For patients with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemotherapy and radiotherapy has resulted in better survival than treatment with radiotherapy alone. Multiple daily fractions of radiotherapy have not resulted in improved survival compared with standard fractionation once daily. Concurrent chemoradiotherapy appears to be associated with improved survival compared with sequential chemotherapy and radiotherapy. Treatment of stage IIIB due to malignant pleural effusion is addressed in the section that deals with stage IV disease.

Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. Controversy abounds as to the optimal treatment of the various stage IIIA subsets, which is fueled by a lack of meaningful, large randomized trials. Multimodality therapy of some type appears to be preferable in stage IIIA patients.

Based on clinical assessment alone, patients with stage II non-small cell lung cancer (NSCLC) comprise only 5% of all patients with NSCLC. In addition, patients with stage II NSCLC represent a heterogeneous group, since stage II consists of patients with T1-2N1 or T3N0 tumors. By definition, patients with tumor invading the chest wall apex, mediastinum, diaphragm, or even the mainstem bronchus may all have T3 tumors. The extent of the data available regarding treatment of each of these different groups is therefore limited. The quality of the data is limited as well, because information often comes from small series of patients. Studies of adjuvant therapy after complete resection of stage II NSCLC are an important exception to this generalization, since data from large, randomized studies of adjuvant radiation therapy, chemotherapy, or a combination of the two are available for analysis. Superior sulcus tumors are discussed elsewhere in these guidelines.

The American Joint Committee on Cancer defines stage I non-small cell lung carcinoma (NSCLC) as consisting of patients with a T1 or T2 primary tumor designation and no evidence of hilar or mediastinal nodal disease (N0) or metastatic spread (M0). Medically fit patients in this clinical stage category based on conventional staging techniques should be considered for aggressive local therapy, and curative treatment is possible. Surgical resection is the accepted treatment for patients with this stage grouping, and full lobar or greater (lobectomy, pneumonectomy) rather than sublobar (wedge resection, segmentectomy) resection is strongly suggested. There is insufficient data to suggest that one method of resection (open thoracotomy, minimally invasive techniques) is superior to another. The performance of a systematic sampling or full mediastinal lymph node dissection may improve pathologic staging but is unproven therapeutically. There are no data supporting the routine use of chemotherapy in an adjuvant or neoadjuvant setting; however, recent phase II data suggest that neoadjuvant chemotherapy is feasible and safe, and larger phase III trials are now evaluating this modality. Primary radiation therapy should be considered for inoperable patients. The use of neoadjuvant or adjuvant radiation therapy in patients with stage I NSCLC is of unproven benefit.

Photodynamic therapy (PDT), brachytherapy, electrocautery, cryotherapy, and Nd-YAG laser therapy are therapeutic options available for management of endobronchial malignancies. All of these treatment modalities have been used for both palliation of late obstructing cancers, and more recently have been used as primary treatment of early radiographically occult cancers. We reviewed the evidence for the use of these treatment options in the management of early lung cancer.

A variety of invasive staging tests are available, including mediastinoscopy, thoracoscopy (video-assisted thoracoscopic surgery), transbronchial needle aspiration (TBNA), transthoracic needle aspiration (TTNA), and endoscopic ultrasound with fine needle aspiration (EUS-NA). Each of these tests requires specific skills, has particular risks, and has technical considerations making it more or less suitable for masses in particular locations. Therefore, direct comparisons among the tests are not possible, and the issue is to define which procedure is most useful for a particular situation. Invasive staging procedures are sometimes used to confirm the stage of a lung cancer, ie, when radiographic staging is not reliable. However, invasive staging procedures are also often used to confirm the diagnosis (ie, when the radiographic stage is reliable). The first situation requires a test with a low false-negative rate; the latter requires a test with high sensitivity. Clinicians must be clear about the question at hand and how to assess the value of a test when selecting an invasive staging procedure. When confirmation of the diagnosis is the primary issue, TBNA (or EUS-NA, if available) are good choices because of high sensitivity and low morbidity. When the primary issue is to confirm that there is no involvement of mediastinal lymph nodes, mediastinoscopy appears to be best suited to most situations. When the primary goal is to confirm malignant involvement of mediastinal nodes, mediastinoscopy also appears to be best in general, although TBNA, TTNA, and EUS-NA may be reasonable alternatives in certain situations. However, selection of a test will also depend on the local availability of expertise, and patient-specific anatomic and physiologic considerations. Selection of the optimal approach is best achieved through a multidisciplinary discussion so that all aspects can be weighed appropriately.

To determine the test performance characteristics of transbronchial needle aspiration (TBNA), transthoracic needle aspiration (TTNA), endoscopic ultrasound-guided needle aspiration (EUS-NA), and mediastinoscopy in staging non-small cell lung cancer (NSCLC).

Correctly staging lung cancer is extremely important because the treatment options and the prognosis differ significantly by stage. Several noninvasive imaging studies are available to aid in identifying disease both within and outside of the chest. Chest CT scanning is useful in providing anatomic detail that better identifies the location of the tumor, its proximity to local structures, and whether or not lymph nodes in the mediastinum are enlarged. Unfortunately, the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is unacceptably low. Whole-body positron emission tomography (PET) scanning provides functional information on tissue activity and has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum. In addition, metastatic disease can be detected by PET scan. Still, positive findings of PET scans can occur from nonmalignant etiologies (eg, infections), so that tissue sampling to confirm the suspected malignancy must be performed. The clinical evaluation tool, which is composed of a thorough history and physical examination, remains the best predictor of metastatic disease. If the findings from the clinical evaluation are negative, then imaging studies such as a CT scan of the head, a bone scan, or an abdominal CT scan are unnecessary, and the search for metastatic disease is complete. If signs, symptoms, or findings from the physical examination suggest the presence of malignancy, then sequential imaging, starting with the most appropriate study based on the clues obtained by the clinical evaluation, should be performed. Abnormalities detected by all of the aforementioned imaging studies are not always cancer. Unless overwhelming evidence of metastatic disease is present on an imaging study, in situations in which it will make a difference in treatment, all abnormal scan findings require tissue confirmation of malignancy so that patients are not precluded from having potentially curative surgery.

To determine the test performance characteristics of CT scanning, positron emission tomography (PET) scanning, MRI, and endoscopic ultrasound (EUS) for staging the mediastinum, and to evaluate the accuracy of the clinical evaluation (ie, symptoms, physical findings, or routine blood test results) for predicting metastatic disease in patients in whom non-small cell lung cancer or small cell lung cancer is diagnosed.