Objective: To evaluate the impact of asthma on patients in Brazil, by age group (12-17 years, 18-40 years, and ≥ 41 years). Methods: From a survey conducted in Latin America in 2011, we obtained data on 400 patients diagnosed with asthma and residing in one of four Brazilian state capitals (São Paulo, Rio de Janeiro, Curitiba, and Salvador). The data had been collected using a standardized questionnaire in face-to-face interviews. For the patients who were minors, the parents/guardians had completed the questionnaire. The questions addressed asthma control, number of hospitalizations, number of emergency room visits, and school/work absenteeism, as well as the impact of asthma on the quality of life, sleep, and leisure. We stratified the data by the selected age groups. Results: The proportions of patients who responded in the affirmative to the following questions were significantly higher in the 12- to 17-year age group than in the other two groups: "Have you had at least one episode of severe asthma that prevented you from playing/exercising in the last 12 months?" (p = 0.012); "Have you been absent from school/work in the last 12 months?" (p < 0.001); "Have you discontinued your asthma relief or control medication in the last 12 months?" (p = 0.008). In addition, 30.2% of the patients in the 12- to 17-year age group reported that normal physical exertion was very limiting (p = 0.010 vs. the other groups), whereas 14% of the patients in the ≥ 41-year age group described social activities as very limiting (p = 0.011 vs. the other groups). Conclusions: In this sample, asthma had a greater impact on the patients between 12 and 17 years of age, which might be attributable to poor treatment compliance.

Keywords: Asthma; Age groups; Quality of life.

Objective: To provide an update on trends in asthma mortality in Brazil for two age groups: 0-4 years and 5-34 years. Methods: Data on mortality from asthma, as defined in the International Classification of Diseases, were obtained for the 1980-2014 period from the Mortality Database maintained by the Information Technology Department of the Brazilian Unified Health Care System. To analyze time trends in standardized asthma mortality rates, we conducted an ecological time-series study, using regression models for the 0- to 4-year and 5- to 34-year age groups. Results: There was a linear trend toward a decrease in asthma mortality in both age groups, whereas there was a third-order polynomial fit in the general population. Conclusions: Although asthma mortality showed a consistent, linear decrease in individuals ≤ 34 years of age, the rate of decline was greater in the 0- to 4-year age group. The 5- to 34-year group also showed a linear decline in mortality, and the rate of that decline increased after the year 2004, when treatment with inhaled corticosteroids became more widely available. The linear decrease in asthma mortality found in both age groups contrasts with the nonlinear trend observed in the general population of Brazil. The introduction of inhaled corticosteroid use through public policies to control asthma coincided with a significant decrease in asthma mortality rates in both subsets of individuals over 5 years of age. The causes of this decline in asthma-related mortality in younger age groups continue to constitute a matter of debate.

Keywords: Asthma/epidemiology; Asthma/mortality; Asthma/drug therapy.

Objective: There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. Methods: A cross-sectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. Results: The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. Conclusions: In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.

Keywords: Asthma; Anxiety; Depression; Cross-sectional studies.

Objective: To evaluate the impact of asthma on activities of daily living and on health status in patients with controlled, partially controlled, or uncontrolled asthma in Brazil. Methods: We used data related to 400 patients in four Brazilian cities (São Paulo, Rio de Janeiro, Salvador, and Curitiba), obtained in a survey conducted throughout Latin America in 2011. All study subjects were > 12 years of age and completed a standardized questionnaire in face-to-face interviews. The questions addressed asthma control, hospitalizations, emergency room visits, and school/work absenteeism, as well as the impact of asthma on the quality of life, sleep, and leisure. The level of asthma control was determined in accordance with the Global Initiative for Asthma criteria. Results: Among the 400 respondents, asthma was controlled in 37 (9.3%), partially controlled in 226 (56.5%), and uncontrolled in 137 (34.2%). The numbers of patients with uncontrolled or partially controlled asthma who visited the emergency room, who were hospitalized, and who missed school/work were higher than were those of patients with controlled asthma (p = 0.001, p = 0.05, and p = 0.01, respectively). Among those with uncontrolled asthma, the impact of the disease on activities of daily living, sleep, social activities, and normal physical exertion was greater than it was among those with controlled or partially controlled asthma (p < 0.001). Conclusions: In Brazil, asthma treatment should be monitored more closely in order to increase treatment adherence and, consequently, the level of asthma control, which can improve patient quality of life and minimize the negative impact of the disease.

Asthma is characterized by variable airflow obstruction, hyperresponsiveness of airways to endogenous or exogenous stimuli and inflammation. Inadequacy of the techniques to use different inhalation devices is a cause of no response to treatment. The main purpose of this study was to evaluate how 20 medical students, 36 resident physicians on Internal Medicine/Pediatrics, and 40 asthma patients used three devices for inhalation therapy containing placebo. All patients were followed at the Pulmonary Outpatient Service of Botucatu Medical School and had been using inhaled medication during the last six months. The following devices were evaluated: metered dose inhalers (MDI), dry powder inhalers (DPI), and MDI attached to a spacer device. A single observer applied a protocol containing the main steps necessary to obtain a good inhaler technique to follow and grade the use of different devices. Health care professionals tested all three devices and patients tested only the device being used on their management. MDI was the device best known by doctors and patients. MDI use was associated with errors related to the coordination between inspiration and device activation. Failure do exhale completely before inhalation of the powder was the more frequent error observed with DPI use. In summary, patients have not been receiving repeated instruction on how to use inhaled medication and health care professionals are not well prepared to adequately teach their patients.

Objective: To identify, characterize, and quantify associations of various factors with quality of life (QoL) in patients with asthma, according to the pharmacotherapy employed. Methods: This was a cross-sectional study involving 49 patients (≥ 18 years of age) with severe uncontrolled or refractory asthma treated at a specialized outpatient clinic of the Brazilian Unified Health Care System, regularly using high doses of inhaled corticosteroids (ICs) or other medications, and presenting comorbidities. At a single time point, QoL was assessed with the Asthma Quality of Life Questionnaire (AQLQ). The overall AQLQ score and those of its domains were correlated with demographic variables (gender and age); Asthma Control Questionnaire score; pharmacotherapy (initial IC dose, inhaler devices, and polytherapy); and comorbidities. Results: Better AQLQ scores were associated with asthma control-overall (OR = 0.38; 95% CI: 0.004-0.341; p < 0.001), "symptoms" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001), and "emotional function" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001)-and with IC dose ≤ 800 µg-"activity limitation" domain (OR = 0.249; 95% CI: 0.070-0.885; p = 0.029). Worse AQLQ scores were associated with polytherapy-"activity limitation" domain (OR = 3.651; 95% CI: 1.061-12.561; p = 0.036)-and number of comorbidities ≤ 5-"environmental stimuli" domain (OR = 5.042; 95% CI: 1.316-19.317; p = 0.015). Conclusions: Our results, the importance of this issue, and the lack of studies taking pharmacotherapy into consideration warrant longitudinal studies to establish a causal relationship between the identified factors and QoL in asthma patients.

Keywords: Asthma; Asthma/drug therapy; Quality of life; Medication therapy management.

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Keywords: Bronchoscopy; Tuberculosis, pulmonary; Sputum; Bronchoalveolar lavage; Biopsy.

Objective: To evaluate the effect of a short-term individualized education program on adherence to asthma treatment, inhalation techniques, and asthma control. Methods: A prospective study involving patients aged 14 years or older, with a confirmed diagnosis of asthma and recruited from the asthma outpatient clinic of a university hospital in the city of Porto Alegre, Brazil. The study was conducted in two phases (before and after the educational intervention). At a routine medical visit, the participants completed a general questionnaire in order to assess the level of asthma control and inhalation techniques. The participants also underwent pulmonary function testing. Subsequently, they participated in an asthma education program, which consisted of one individualized session. The participants were reevaluated after three months. Results: Of the 174 patients recruited, 115 completed the study. Between the first and second evaluations, there was a significant improvement in the effective use of inhaled corticosteroids (90.4% vs. 93.3%; p = 0.003), the effective use of long-acting β2 agonists (57.4% vs. 63.5%; p < 0.0001), the effective use of a combined regimen with these two medications (57.4% vs. 62.6%; p < 0.0001), and the self-reported adherence to corticosteroid therapy (p = 0.001). There was a significant decrease in the proportion of patients visiting ERs (30.4% vs. 23.5%; p = 0.012). However, the level of asthma control and the inhalation technique did not improve significantly (p = 0.095 and p = 0.512, respectively). Conclusions: This short-term asthma education program resulted in an improvement in the use of medications for asthma control and a decrease in the number of ER visits, although it had no significant effect on the inhalation technique.

Keywords: Ambulatory care; Patient education as topic; Respiratory therapy; Metered dose inhalers.

Objective: To determine whether the predictive accuracy of clinical judgment alone can be improved by supplementing it with an objective weaning protocol as a decision support tool. Methods: This was a multicenter prospective cohort study carried out at three medical/surgical ICUs. The study involved all consecutive difficult-to-wean ICU patients (failure in the first spontaneous breathing trial [SBT]), on mechanical ventilation (MV) for more than 48 h, admitted between January of 2002 and December of 2005. The patients in the protocol group (PG) were extubated after a T-piece weaning trial and were compared with patients who were otherwise extubated (non-protocol group, NPG). The primary outcome measure was reintubation within 48 h after extubation. Results: We included 731 patients-533 (72.9%) and 198 (27.1%) in the PG and NPG, respectively. The overall reintubation rate was 17.9%. The extubation success rates in the PG and NPG were 86.7% and 69.6%, respectively (p < 0.001). There were no significant differences between the groups in terms of age, gender, severity score, or pre-inclusion time on MV. However, COPD was more common in the NPG than in the PG (44.4% vs. 17.6%; p < 0.001), whereas sepsis and being a post-operative patient were more common in the PG (23.8% vs. 11.6% and 42.4% vs. 26.4%, respectively; p < 0.001 for both). The time on MV after the failure in the first SBT was higher in the PG than in the NPG (9 ± 5 days vs. 7 ± 2 days; p < 0.001). Conclusions: In this sample of difficult-to-wean patients, the use of a weaning protocol improved the decision-making process, decreasing the possibility of extubation failure.

Keywords: Ventilator weaning; Ventilation; Ventilators, mechanical.

Objective: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. Methods: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. Results: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. Conclusions: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

Keywords: Breast neoplasms; Radiotherapy; Radiation pneumonitis; Respiratory function tests; Exercise test.

Objective: To investigate the impact of a pulmonary rehabilitation program on the functional capacity and on the quality of life of patients on waiting lists for lung transplantation. Methods: Patients on lung transplant waiting lists were referred to a pulmonary rehabilitation program consisting of 36 sessions. Before and after the program, participating patients were evaluated with the six-minute walk test and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The pulmonary rehabilitation program involved muscle strengthening exercises, aerobic training, clinical evaluation, psychiatric evaluation, nutritional counseling, social assistance, and educational lectures. Results: Of the 112 patients initially referred to the program, 58 completed it. The mean age of the participants was 46  14 years, and females accounted for 52%. Of those 58 patients, 37 (47%) had pulmonary fibrosis, 13 (22%) had pulmonary emphysema, and 18 (31%) had other types of advanced lung disease. The six-minute walk distance was significantly greater after the program than before (439 ± 114 m vs. 367 ± 136 m, p = 0.001), the mean increase being 72 m. There were significant point increases in the scores on the following SF-36 domains: physical functioning, up 22 (p = 0.001), role-physical, up 10 (p = 0.045); vitality, up 10 (p < 0.001); social functioning, up 15 (p = 0.001); and mental health, up 8 (p = 0.001). Conclusions: Pulmonary rehabilitation had a positive impact on exercise capacity and quality of life in patients on lung transplant waiting lists.

Keywords: Rehabilitation; Lung transplantation; Quality of life; Exercise; Exercise tolerance.

Objective: To quantify the use of health care resources among patients enrolled in the Bahia State Asthma and Allergic Rhinitis Control Program. Methods: As of January of 2006, 1405 patients had enrolled in the program, which is carried out in four referral centers in the city of Salvador. These patients formed the basis of this retrospective/prospective, observational cohort study. The preliminary analysis involved 269 consecutive patients, all above the age of 12 and diagnosed with severe asthma. After being seen by pulmonologists, nurses, pharmacologists and psychologists, the patients received inhaled asthma medications. Based on patient interviews and charts, the year preceding enrollment in the program was compared with the first year enrolled in the program in terms of the following quantifiable parameters: hospital admissions; emergency room visits; courses of oral corticosteroids; and days of school/work missed due to asthma attacks. Results: In this sample of patients with severe asthma, enrollment in the program resulted in significant reductions in the number of emergency room visits and hospital admissions (of 85% and 90%, respectively). There were also reductions in the number of school/work days missed due to asthma attacks and in the number of courses of oral corticosteroids (of 86% and 67%, respectively). Conclusion: A program designed to control severe asthma in referral outpatient clinics and including pharmacological services at no charge can lead to a pronounced reduction in the demand for Unified Health Care System resources.

Keywords: Asthma/therapy; Asthma/prevention  control; Hospitalization; National Health System (BR)

For diagnostic purposes of pleural tuberculosis, three pleural fragments are routinely obtained from a single site by needle biopsy. The objective of this study is to compare the diagnostic yield of the routine procedure with two different approaches: harvesting five fragments on a single site (A), and collection of fragments at an additional site (B); from the same cutaneous orifice, the needle was partially removed up to the subcutaneous tissue and redirected at a 45o angle. The authors performed a prospective study in 115 patients submitted to pleural biopsy. The first three pleural fragments were placed in a vial (VA1-3), the 5 subsequent fragments obtained at the same site were placed in a second vial (VA4-8), and the five fragments from the second site were placed in a third vial (VB1-5). Analysis of fragments from VA1-3 revealed granuloma in 72/92 tuberculosis cases (78.3%), whereas in fragments VA5-8 and VB1-5, granuloma was observed in 74/92 cases (80.5%). In 6/92 patients the diagnosis at VA1-3 was non-specific pleuritis, but granuloma was found in VA4-8, resulting in a diagnosis increment of 8.3% (adding six to the 72 patients). In 7/92 patients (7.6%) the histopathological examination at site A led to a non-specific result but granuloma was found at site B, leading to a diagnostic increment of 9.0% (7 to 78 patients). Histological concordance of two examinations by the same pathologist had a kappa index of 0.62 (0.54 to 0.7) whereas concordance between two different pathologists had a kappa index of 0.64 (0.56 to 0.72). The performance of multiple biopsies at two different sites at the pleural surface led to an additional diagnosis of 13 patients, i.e., an increase of 18% (13 to 72) relative to the routine procedure. Considering the low cost increase of obtaining the fragments, adoption of this method is recommended in routine pleural tuberculosis diagnosis.

Keywords: Tuberculosis, pleural tuberculosis, biopsy, diagnosis.

The objective of this study was to review the literature, focusing on difficulties encountered in asthma diagnosis and in the establishment of initial inhaled corticosteroid treatment in children under five years of age. The search was limited to studies published between 1991 and 2002 in Portuguese, Spanish, or English and included in the LILACS and MEDLINE databases. Symptoms of asthma, the most common chronic childhood disease, typically appear in the first years of life. There are currently no diagnosis means of making a certain diagnosis of asthma in children under the age of five. Clinical manifestations, when present in toddlers and preschoolers, may require treatment such as that given for asthma, assuming that it is preceded by a critical evaluation. We can conclude that diagnosis of asthma in the first years of life is complex and predominantly clinical. Inhaled corticosteroid treatment is an effective tool, although its risks and benefits must be carefully evaluated.

Keywords: Asthma. Adrenal cortex hormones. Infant. Preschool.

Objective: Asthma and respiratory symptoms are common in children, and many studies have shown associations between childhood symptoms and impaired lung function in adult life. The aim of the present study was to investigate the association of various respiratory symptoms with wheezing patterns (persistent, early, and late-onset) and lung function, as well as to determine whether lung function was associated with atopy or with demographic, socioeconomic, environmental, and gestational factors, in a birth cohort at 6-7 years of age. Methods: The target population consisted of children aged 6-7 years from a birth cohort of 5,304 children born in southern Brazil in 1993. For this follow-up evaluation, 532 of those children were randomly selected, and a sub-sample was submitted to spirometry and skin prick tests. A questionnaire was administered to the parent(s) or legal guardian(s) of each child. Results: Spirometric values were lower in the children with respiratory symptoms or asthma. Mean forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC ratio) was lower in children with any of the following: current wheezing and asthma; asthma ever; four or more episodes of wheezing within the preceding 12 months; sleep disturbance due to wheezing; and exercise-induced wheezing. Persistent wheezing was associated with lower FEV1/FVC ratio. After multiple linear regression, exercise-induced wheezing was also associated with reduced FEV1/FVC ratio. Nonwhite skin color and wheezing severe enough to limit speech were associated with lower FEV1. Conclusions: Children with persistent wheezing and symptoms of severe asthma have impaired lung function at 6-7 years of age.

Keywords: Asthma; Respiratory function tests; Respiratory sounds; Signs and symptoms, respiratory.

Objective: To evaluate the management of asthma attacks in children up to five years of age treated in the pediatric emergency room of a hospital in the metropolitan area of the city of Recife, Brazil, as well as to determine whether the way in which asthma attacks are managed can influence the duration of emergency room visits for such children. Methods: A descriptive, exploratory study employing a quantitative, cross-sectional approach. The study sample comprised 246 children treated for asthma attacks in an emergency room. The approach used was evaluated in comparison with the approach recommended in the III Brazilian Consensus on Asthma Management, as was the length of time each child spent in the emergency room. Results: In 69 (28.1%) of the cases, the medications were used in accordance with the Consensus guidelines. In 34 (13.8%) of the cases, the doses used were those recommended in the Consensus guidelines, and the guidelines regarding nebulization procedures were followed in 33 cases (13.4%). No correlation was found between the approach taken and the length of the emergency room visit. In the logistic regression analysis, we observed that the adjusted risk of being released from the emergency room sooner than recommended in the Consensus guidelines (a length of time sufficient to allow the response to the treatment to be analyzed) was four times and fifteen times greater, respectively, for children with mild persistent asthma and for those with intermittent asthma. Conclusion: Although there are obstacles to using the asthma management approach recommended in the Consensus guidelines (such obstacles including the lack of familiarity with the guidelines on the part of the multidisciplinary team, as well as the lack of recommended material and therapeutic resources), the duration of emergency room visits was found to be related to the degree of asthma severity.

Keywords: Emergency medicine; Pediatrics; Asthma; Status asthmaticus

Objective: To assess the agreement among asthma control measures and functional exercise capacity in children and adolescents with uncontrolled and controlled asthma. Methods: Children and adolescents with asthma from 7-17 years old were selected, and they were attended in the "Pediatric Pulmonology Outpatient Clinic of State University of Campinas", in Brazil. All patients had asthma control level assessed by Global Initiative for Asthma questionnaire (GINAq), Asthma Control Test (ACT), spirometry and six-minute-walk-test (6MWT). Patients were classified as uncontrolled or controlled asthma in each test and agreement among measures was assessed by kappa statistics. The ROC curve was calculated for the 6MWT. The spirometric index obtained from spirometry was composed by FEV1, FEV1/FVC and FEF25-75%. Spirometry and 6MWT results were compared between uncontrolled and controlled asthma group by GINAq. Results: Of the 138 subjects included, 78 (56.5%) were male with median age of 11 (7-17) years old. GINAq detected 68.8% of patients with uncontrolled asthma. Moderate agreement (p < 0.001; k = 0.56) and high specificity (100%) was observed between GINAq and ACT. In 6MWT, the cut-off point of 82.03% of predicted distance was able to distinguish patients with controlled and uncontrolled asthma. Spirometric index presented 73.4% of sensitivity according to GINAq. The results for 6MWT in patients with uncontrolled asthma were the worst of all. Conclusion: This study highlights the importance of assessing more than one measure to differentiate asthma control level. GINAq identified more patients with uncontrolled asthma and presented moderate agreement with ACT. Spirometric index was associated with uncontrolled asthma according to GINAq. 6MWT was a suitable measure to distinguish patients with controlled and uncontrolled asthma.

Keywords: Asthma; Asthma control; Spirometry; Walk test; Children.

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Keywords: Neoplasms; Lymphangioleiomyomatosis/therapy; TOR serine-threonine kinases; Sirolimus.