Ventilator-associated tracheobronchitis: the impact of targeted antibiotic therapy on patient outcomes

Nosocomial lower respiratory tract infections are a common cause of morbidity and mortality in ICU patients receiving mechanical ventilation. Many studies have investigated the management and prevention of ventilator-associated pneumonia (VAP), but few have focused on the role of ventilator-associated tracheobronchitis (VAT). The pathogenesis of lower respiratory tract infections often begins with tracheal colonization that may progress to VAT, and in selected patients to VAP. Since there is no well-established definition of VAT, discrimination between VAT and VAP can be challenging. VAT is a localized disease with clinical signs (fever, leukocytosis, and purulent sputum), microbiologic information (Gram stain with bacteria and leukocytes, with either a positive semiquantitative or a quantitative sputum culture), and the absence of a new infiltrate on chest radiograph. Monitoring endotracheal aspirates has been used to identify and quantify pathogens colonizing the lower airway, to diagnose VAT or VAP, and to initiate early, targeted antibiotic therapy. Recent data suggest that VAT appears to be an important risk factor for VAP and that targeted antibiotic therapy for VAT may be a new paradigm for VAP prevention and better patient outcomes.     

Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic administration rule

BACKGROUND: The 2003 Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend the initiation of antibiotic therapy within 4 h of hospitalization. This quality indicator has been linked to the incentive compensation of third-party payers to hospitals. We evaluated the impact of this recommendation on the diagnosis of CAP and the utilization of antibiotics. METHODS: All patients with a hospital admission diagnosis of CAP before publication of the guidelines (January to June 2003) and after publication of the guidelines (January-June 2005) were included. We collected data on clinical signs and symptoms on presentation, chest radiograph findings, blood cultures prior to therapy with antibiotics, time to antibiotic administration, pneumonia severity index (PSI) score, confusion, urea, respiratory rate, BP, and age >or= 65 years (CURB-65), and mortality. RESULTS: A total of 518 patients were included in the study. More patients in 2005 had a hospital admission diagnosis of CAP without radiographic abnormalities compared to 2003 (2005, 91 patients [28.5%]; 2003, 41 patients [20.6%]; p = 0.04), and more patients received antibiotics within 4 h of triage (2005, 210 patients [65.8%]; 2003, 107 patients [53.8%]; p = 0.007). Blood cultures prior to antibiotic administration increased (2005, 220 patients [69.6%]; 2003, 93 patients [46.7%]; p < 0.001). However, the final diagnosis of CAP dropped to 58.9% in 2005 from 75.9% in 2003 (p < 0.001). The mean (+/- SD) antibiotic utilization per patient increased to 1.66 +/- 0.54 in 2005 compared to 1.39 +/- 0.58 in 2003 (p < 0.001). There were no significant differences in PSI or CURB-65 scores, or mortality. CONCLUSIONS: Linking antibiotic administration within 4 h of hospital admission (as a quality indicator) to financial compensation may result in an inaccurate diagnosis of CAP, inappropriate utilization of antibiotics, and thus less than optimal care.     

Recent advances in community-acquired pneumonia: inpatient and outpatient

Community-acquired pneumonia (CAP) is a common illness, with the majority of patients treated out of the hospital, yet the greatest burden of the cost of care comes from inpatient management. In the past several years, the management of these patients has advanced, with new information about the natural history and prognosis of illness, the utility of serum markers to guide management, the use of appropriate clinical tools to guide the site-of-care decision, and the finding that guidelines can be developed in a way that improves patient outcome. The challenges to patient management include the emergence of new pathogens and the progression of antibiotic resistance in some of the common pathogens such as Streptococcus pneumoniae. Few new antimicrobial treatment options are available, and the utility of some new therapies has been limited by drug-related toxicity. Ancillary care for severe pneumonia with activated protein C and corticosteroids is being studied, but recently, inpatient care has been most affected by the development of evidence-based "core measures" for management that have been promoted by the Centers for Medicare and Medicaid Services, which form the basis for the public reporting of hospital performance in CAP care.     

Management of community-acquired pneumonia in the home: an American College of Chest Physicians clinical position statement

The number of patients with community-acquired pneumonia (CAP) who are being treated at home is increasing for a variety of reasons. These reasons include the increased availability and cost considerations of oral antibiotics that have been shown to be effective, as well as the consideration of patient and family preferences. However, there is still considerable variability in strategies for the management of patients with CAP. This American College of Chest Physicians position statement, which was cosponsored by the American Academy of Home Care Physicians, provides recommendations on the various aspects of home care for patients with this condition. Included are recommendations for evaluation and diagnosis in the home environment and the determination of the site of care, and an outline of an in-home management plan. The position statement also provides recommendations for issues related to patient and caregiver commitment to the plan, and for monitoring and follow-up. Recommendations are directed toward immunocompetent adult patients with CAP who are at home or in other unskilled residential facilities. These patients can include previously healthy individuals or chronically ill individuals who choose not to go to the hospital, or hospitalized patients who are completing a hospital discharge plan. The recommendations in this statement take into consideration the best course of action for the patient, as determined by incorporating the most recent evidence with clinician judgment and patient preferences. These recommendations also consider the available resources. Therefore, these recommendations may not apply to every patient, and interventions may need to be structured based on the individual. In addition to providing recommendations for the home care management of patients with CAP, we hope that this clinical policy statement will alert readers to the need for more scientific evidence related to the clinical and psychosocial issues associated with managing this condition.     

Comparison of outcomes for low-risk outpatients and inpatients with pneumonia: A propensity-adjusted analysis

BACKGROUND: Low-risk patients with community-acquired pneumonia are often hospitalized despite guideline recommendations for outpatient treatment. METHODS: Using data from a randomized trial conducted in 32 emergency departments, we performed a propensity-adjusted analysis to compare 30-day mortality rates, time to the return to work and to usual activities, and patient satisfaction with care between 944 outpatients and 549 inpatients in pneumonia severity index risk classes I to III who did not have evidence of arterial oxygen desaturation, or medical or psychosocial contraindications to outpatient treatment. RESULTS: After adjusting for quintile of propensity score for outpatient treatment, which eliminated all significant differences for baseline characteristics, outpatients were more likely to return to work (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.5 to 2.6) or, for nonworkers, to usual activities (OR, 1.4; 95% CI, 1.1 to 1.8) than were inpatients. Satisfaction with the site-of-treatment decision (OR, 1.1; 95% CI, 0.7 to 1.8), with emergency department care (OR, 1.4; 95% CI, 0.9 to 1.9), and with overall medical care (OR, 1.1; 95% CI, 0.8 to 1.6) was not different between outpatients and inpatients. The overall mortality rate was higher for inpatients than outpatients (2.6% vs 0.1%, respectively; p < 0.01); the mortality rate was not different among the 242 outpatients and 242 inpatients matched by their propensity score (0.4% vs 0.8%, respectively; p = 0.99). CONCLUSIONS: After adjusting for the propensity of site of treatment, outpatient treatment was associated with a more rapid return to usual activities and to work, and with no increased risk of mortality. The higher observed mortality rate among all low-risk inpatients suggests that physician judgment is an important complement to objective risk stratification in the site-of-treatment decision for patients with pneumonia.     

The effect of body mass index on patient outcomes in a medical ICU

STUDY OBJECTIVES: To examine the effect of patient body mass index (BMI) on outcome in intensive care. DESIGN: In a prospective study, the patients were classified into groups based on the calculated BMI, as follows: BMI < 19.0 (n = 350), > or = 19.0 and < 25.0 (n = 663), > or = 25.0 and < 29.9 (n = 585), > or = 30.0 and < 40.0 (n = 396), and > or = 40.0 (n = 154). Groups were compared by age, APACHE (acute physiology and chronic health evaluation) II score, mortality, ICU length of stay (LOS), hospital LOS, number receiving ventilation, and ventilator-days. Adverse events including nosocomial pneumonia, ventilator-days per patient, failed extubations, and line-related complications were recorded. SETTING: The study was conducted in a 9-bed medical ICU of a 650-bed tertiary care hospital. MEASUREMENTS: Height and weight were prospectively recorded for the first ICU admission during a hospital stay. RESULTS: Between January 1, 1997, and August 1, 2001, 2,148 of 2,806 patients admitted to the ICU had height and weight recorded. There were no differences in APACHE II score, mortality, ICU LOS, hospital LOS, number receiving ventilation, ventilator-days, average total cost, or average variable cost among the five groups. However, the severely obese patients were more frequently female and younger than those who were overweight and obese (p < 0.001). Adverse events were infrequent, but there were no differences between the obese/very obese compared with others. CONCLUSION: BMI has minimal effects on ICU outcome after patients are admitted to a critical care unit.     

The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort study

BACKGROUND: It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS: We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS: We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS: Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.     

The modified APACHE II score outperforms Curb65 pneumonia severity score as a predictor of 30-day mortality in patients with methicillin-resistant Staphylococcus aureus pneumonia

OBJECTIVE: To compare the predictive accuracy for 30-day mortality of the CURB65 score adopted by the British Thoracic Society and the simpler CRB65 score to APACHE (acute physiology and chronic health evaluation) II in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization identified to have MRSA pneumonia. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Two hundred eighteen patients with MRSA pneumonia were identified over a 3-year period. Forty-four patients (20.2%) died during hospitalization. All three prediction rules had high negative predictive values but relatively low positive predictive values at most cut-off points examined. APACHE II had the greatest area under the receiver operating characteristic curve (0.805; 95% confidence interval [CI], 0.743 to 0.866) compared to CURB65 (0.634; 95% CI, 0.541 to 0.727) and CRB65 (0.643; 95% CI, 0.546 to 0.739) [p < 0.05 for both comparisons]. Similar results were obtained when the subgroups of community-acquired MRSA pneumonia and health-care-associated MRSA pneumonia were examined separately. CONCLUSIONS: APACHE II outperformed CURB65 and CRB65 for initial prognostic assessment in MRSA pneumonia.     

Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease

STUDY OBJECTIVES: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia. DESIGN: Retrospective review. SETTING: Two thousand-bed, university-affiliated, tertiary referral center. PATIENTS: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD. METHOD: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared. RESULTS: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively. CONCLUSIONS: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.     

Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens

BACKGROUND AND STUDY OBJECTIVES: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. METHODS: We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses. RESULTS: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients >/= 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). CONCLUSIONS: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP.     

A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU

BACKGROUND: Limited information is available on the health-care utilization of hospitalized patients with community-acquired pneumonia (CAP) depending on the location of care. Our aim was to compare the clinical characteristics, etiologies, and outcomes of patients with CAP who were admitted to the ICU with those admitted who were to the ward service. METHODS: A retrospective cohort study, at two tertiary teaching hospitals, one of which was a Veterans Affairs hospital, and the other a county hospital. Eligible subjects had been admitted to the hospital with a diagnosis of CAP between January 1, 1999, and December 31, 2001, had a confirmatory chest radiograph, and a hospital discharge International Classification of Diseases, ninth revision, diagnosis of pneumonia. Subjects were excluded from the study if they had designated "comfort measures only" or had been transferred from another acute care hospital or were nursing home patients. Bivariate and multivariable analysis evaluated 30-day and 90-day mortality as the dependent measures. RESULTS: Data were abstracted on 730 patients (ICU, 145 patients; wards, 585 patients). Compared to ward patients, ICU patients were more likely to be male (p = 0.001), and to have congestive heart failure (p = 0.01) and COPD (p = 0.01). ICU patients also had higher mean pneumonia severity index scores (112 [SD, 35] vs 83 [SD, 30], respectively; p = 0.02). Patients admitted to the ICU had a longer mean length of hospital stay (12 days [SD, 10 days] vs 7 days [SD, 17 days], respectively; p = 0.07), and a higher 30-day mortality rate (23% vs 4%, respectively; p < 0.001) and 90-day mortality rate (28% vs 8%, respectively; p < 0.001) compared to ward patients. CONCLUSIONS: ICU patients present with more severe disease and more comorbidities. ICU patients stay longer in the hospital and have a much higher mortality rate when compared to ward patients. Management strategies should be designed to improve clinical outcomes in ICU patients.     

Panton-Valentine Leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis

BACKGROUND: Panton-Valentine Leukocidin-expressing (PVL+) methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen worldwide causing fatal necrotizing pneumonias in otherwise healthy individuals but has not been described in patients with cystic fibrosis (CF). Following two cases of patients with CF admitted with lung abscesses in association with PVL+ MRSA, we examined the incidence and the clinical characteristics of MRSA acquisition in our CF patient population. METHODS: Newly acquired MRSA isolates from patients with CF followed up at St. Louis Children's Hospital were analyzed for the presence of Panton-Valentine leukocidin coding region, clindamycin susceptibility, staphylococcal cassette chromosome (SCC) mec type, and multilocus sequence type. Medical records and pulmonary function studies at the time of MRSA isolation were reviewed. RESULTS: MRSA isolates from 40 CF patients were available for analysis. Six children (15%) had PVL+ MRSA infection. All PVL+ organisms were clindamycin susceptible. Patients who acquired a PVL+ organism were more likely to have a focal pulmonary infiltrate on chest radiograph, including cavitary lung lesions in two patients (p = 0.04), a markedly greater decline in FEV1 at the time of MRSA detection (p = 0.01), and a significantly higher WBC count (p = 0.04) and absolute neutrophil count (p = 0.04). These patients were more likely to be admitted for IV antibiotic therapy for respiratory illnesses (p < 0.01). CONCLUSIONS: We describe the emergence of PVL+ MRSA in our CF population in association with development of invasive lung infections including lung abscesses. Early identification and treatment of CF patients with newly acquired PVL+ MRSA may be crucial.     

Diagnosis of nosocomial pneumonia in cancer patients undergoing mechanical ventilation: a prospective comparison of the plugged telescoping catheter with the protected specimen brush.

STUDY OBJECTIVES: Quantitative culture of protected samples of lower respiratory tract secretions obtained by a fiberoptic protected specimen brush (PSB) is widely accepted for the diagnosis of ventilator-associated pneumonia (VAP), but this diagnostic procedure is time consuming, expensive, and may give rise to iatrogenic complications, especially in cancer patients who often present with thrombocytopenia. The plugged telescoping catheter (PTC) could be a satisfactory alternative to the PSB in this setting. The aim of the present study was to evaluate the interest of the PTC to diagnose VAP in ventilated cancer patients. DESIGN: A prospective observational study. SETTING: A 15-bed medical-surgical ICU in a comprehensive cancer center. PATIENTS AND INTERVENTIONS: Over a 9-month period, 42 patients suspected of having bacterial VAP during mechanical ventilation underwent 69 bronchial samplings: a blinded PTC and a fiberoptic PSB were performed successively in each case. A positive culture for both sampling procedures was defined as the recovery of > or = 10(3) cfu/mL of at least one potential pathogen. The PSB result was taken as the reference standard. MEASUREMENTS AND RESULTS: The overall agreement between the techniques was 87% (60/69). PTC had a sensitivity of 67%, a specificity of 93%, a positive predictive value of 71%, and a negative predictive value of 91%. CONCLUSIONS: We conclude that the accuracy of the blinded PTC compares well with that of the PSB for the diagnosis of VAP in cancer patients. The sensitivity of the PTC observed herein, which is slightly lower than that described in previous studies, may be due to the blinded nature of the method: the indications for initial or secondary coupling with a directed sampling method in patients with suspicion of localized pneumonia remain to be determined.     

Alterations in smoking habits are associated with acute eosinophilic pneumonia

BACKGROUND: Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS: We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS: Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION: These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Lymphangioleiomyomatosis: a clinical update

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that is associated with mutations in tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread, and remarkable female gender restriction. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections. Lung function declines at approximately twofold to threefold times the rate of healthy subjects, based on an annual drop in FEV1 of 75 to 120 mL in reported series. The diagnosis of pulmonary LAM can be made on high-resolution CT (HRCT) scan with reasonable certainty by expert radiologists, but generally requires a lung biopsy in cases in which tuberous sclerosis complex, angiomyolipomata, or chylous effusions are absent. The currently available treatment strategies are based on the antagonism of estrogen action, and are empiric and unproven. A trial of bronchodilators is warranted in patients with reversible airflow obstruction seen on pulmonary function testing. Pleurodesis should be performed with the initial pneumothorax, because the rate of recurrence is high. Angiomyolipomas that exceed 4 cm in size are more likely to bleed and should be evaluated for embolization. Air travel is well-tolerated by most patients with LAM. Lung transplantation is an important option for LAM patients, and can be safely performed by experienced surgeons despite prior unilateral or bilateral pleurodesis in most patients. Women with unexplained recurrent pneumothorax, tuberous sclerosis, or a diagnosis of primary spontaneous pneumothorax or emphysema in the setting of limited or absent tobacco use should undergo HRCT scan screening for LAM. Multicenter clinical trials based on several well-defined molecular targets are currently underway in the United States and Europe.