Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

Keywords: Pulmonary hypertension; Vasodilator agents; Calcium channel blockers.

Objective: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH). Methods: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD), significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. Results: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302 patients (78.6%). The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001). Conclusions: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant.

Keywords: Hypertension, pulmonary; Cardiac catheterization, Ventricular dysfunction, left.

Objective: To develop and validate a protocol for the treadmill six-minute walk test (tread6MWT) to evaluate patients with pulmonary arterial hypertension (PAH). Methods: The study population comprised 73 patients with PAH, diagnosed by means of right heart catheterization, with or without NO inhalation. All patients performed a hallway 6MWT and three tread6MWTs based on a pre-determined incremental speed protocol and interposed by a rest period. The patients who had been submitted to hemodynamic testing using NO performed the third tread6MWT while inhaling the same dose of NO that had been used during the catheterization. Results: We found that the treadmill six-minute walk distance (tread6MWD) correlated with hemodynamic data, functional class and the hallway six-minute walk distance (6MWD). In addition, the tread6MWD correlated significantly with survival, thereby confirming the correlation with disease severity. Inhalation of NO during the tread6MWT led to variations that were consistent with the hemodynamic changes induced by the same dose of inhaled NO, suggesting that the protocol developed can reflect the effect of therapeutic interventions. Conclusions: We conclude that the tread6MWD is a useful prognostic and functional marker for the routine evaluation of PAH patients.

Keywords: Hypertension, pulmonary; Exercise test; Hemodynamics.

Primary pulmonary hypertension is a rare, progressive disease with high mortality rates. The treatment of primary pulmonary hypertension is still based on high-cost drugs, not yet available in developing countries. Recently, the use of sildenafil as an alternative drug for primary pulmonary hypertension treatment has been reported. It is reported a case of a 21 year-old female patient with primary pulmonary hypertension, who presented an acute worsening of symptoms and decrease of oxygen saturation. The investigation revealed the existence of a patent oval foramen not previously seen, with right-to-left shunt. Sildenafil treatment was instituted in escalating doses. After 40 days of treatment, the echocardiogram showed resolution of the shunt, concomitant to oxygenation improvement. The authors believe that sildenafil is a feasible alternative for primary pulmonary hypertension treatment, although larger clinical trials are necessary to determine its clinical safety and efficacy.

Keywords: Pulmonary hypertension/therapy. Vasodilator agents/administration & dosage.

In the atypical smooth muscle cells that are characteristic of lymphangioleiomyomatosis (LAM), there are estrogen and progesterone receptors. Therefore, anti-hormonal therapy, despite having produced controversial results, can be considered a treatment option. The objective of this retrospective study was to evaluate hormonal and spirometric data for nine women with LAM after one year of treatment with goserelin. The mean increase in FEV1 and FVC was 80 mL and 130 mL, respectively. There was effective blockage of the hormonal axis. It is still not possible to exclude a potential beneficial effect of the use of gonadotropin-releasing hormone analogues in LAM patients, which underscores the need for randomized trials.

Keywords: Lymphangioleiomyomatosis; Spirometry; Goserelin.

Objective: Making the differential diagnosis between asthma and chronic obstructive pulmonary disease (COPD) based on the response to inhaled bronchodilators by means of spirometry is controversial.The objective of this study was to identify the most useful spirometric variables in order to distinguish between asthma and COPD. Methods: Retrospective study conducted from April of 2004 to January of 2006, comparing the spirometric parameters of 103 nonsmoking patients with asthma to those of 108 patients with COPD who were smokers for more than 10 pack-years. All of the patients included in the study were older than 40 and presented stable disease at the time of the test. Results: Initial forced expiratory volume in one second (FEV1) was the same in the two groups (pre-bronchodilator FEV1 = 51%). However, patients with COPD were older (66 ± 9 years vs. 59 ± 11 years, p < 0.001) and more frequently male (73% vs. 27%, p < 0,001).After the use of the bronchodilator, the median absolute difference in FEV1 was 0.25 L (range, −0.09 to 1.13 L) in patients with asthma and 0.09 L (range, −0.1 to 0.73 L) in those with COPD (p < 0.001).The highest sensitivity (55%), specificity (91%) and likelihood ratio (6.1) for asthma diagnosis was obtained when the percentage increase in postbronchodilator FEV1 in relation to the predicted FEV1 (Δ%predFEV1) was equal to or greater than 10%.Isolated significant increases in forced vital capacity were more common in patients with COPD. Conclusions: In patients over the age of 40 and presenting obstructive lung disease, a Δ%predFEV1 ≥ 10% is the best spirometric parameter to distinguish asthma from COPD.

Keywords: Spirometry; Respiratory function tests; Lung diseases, obstructive.

Objective: Barriers to physical activity can affect the functional capacity and quality of life of patients with pulmonary hypertension (PH). This study aimed to identify the main barriers to physical activity in patients with PH and to examine whether those barriers are related to functional capacity, echocardiographic variables, or quality of life. Methods: This was a cross-sectional observational study involving 70 patients. Participants scored seven potential barriers to their activities, with a score = 5 indicating a significant barrier. Participants completed the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Manchester Respiratory Activity of Daily Living questionnaire, as well as the six-minute walk test. Correlation analysis, univariate analysis and multiple logistic regression were performed. Results: As a perceived barrier to physical activity, 'lack of will' or 'lack of energy' was cited by 67% of the patients. The 'lack of will' barrier was found to correlate with all SF-36 domains except bodily pain. We also identified a correlation between the SF-36 vitality domain and the barriers 'lack of energy', 'lack of will' and 'lack of structure'. The logistic regression analysis indicated that the vitality domain correlated significantly with the barriers 'social influence', 'lack of energy', 'lack of will', and 'lack of structure'. For each unit decrease in the vitality score, there was a 10% increase in the probability of citing the barrier 'lack of will'. No significant correlations were identified between any of the perceived barriers and echocardiographic parameters. Conclusions: The perceived barrier most commonly reported was 'lack of will/energy', which correlated with almost all SF-36 domains, especially vitality. The 'lack of will' barrier also correlated with functional capacity.

Keywords: Pulmonary arterial hypertension; Exercise; Motivation; Quality of life; Surveys and questionnaires; Walk test.

Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography (HRCT) findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans.

Keywords: Lung diseases, interstitial; Pulmonary fibrosis; Tomography, X-ray computed; Respiratory function tests.

The aim of this study was to analyze the results of 17 patients with myasthenia gravis who, from 1985 to 1994, were submitted to thymectomy at the Medical School of Santa Casa de São Paulo. Nine patients (52.9%) were female and the mean age was approximately 30.3 years. The most usual symptoms were ptoses, weakness, and diplopia. Other symptoms included: dyspnea, dysphonia, thoracic pain and loss of weight. The average development period of the disease was 17.5 months (between 3 and 96 months). The diagnostic methods use were chest X-ray, response to edrophonium chloride (Tensilon), electrophysiologic study and thoracic CT. All patients were submitted to thymectomy through medium sternotomy. Patients were followed up from one month to ten years. Only one patient did not return to the clinic. Twelve patients (75%) achieved good results. The others four patients presented little or no response after thymectomy.

Keywords: Thymectomy. Myasthenia gravis.

Objective: To conduct a cross-cultural adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) as an instrument to evaluate the perception of symptoms, functional limitation, and health-related quality of life (HRQoL) in subjects diagnosed with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Colombia. Methods: The adaptation process involved 3 phases: translation, cognitive debriefing interviews, and a validation survey. To evaluate the psychometric properties, we recruited individuals ≥ 18 years of age who had been diagnosed with PAH or CTEPH to take part in the latter two stages of the adaptation process. All individuals were being followed on an outpatient basis by the pulmonary hypertension programs at Hospital Universitario San Ignacio, Fundación Clínica Shaio,and Clínicos IPS, all located in the city of Bogotá, Colombia. Results: A Spanish-language version of the CAMPHOR was developed for use in Colombia. The internal consistency was excellent for the symptoms, functioning, and quality of life scales (Cronbach's alpha coefficients of 0.92, 0.87, and 0.93, respectively). Test-retest reliability was above 0.70. The evaluation of the convergent validity and known group validity of the CAMPHOR scales confirmed that there were moderate and strong correlations with the related constructs of the Medical Outcomes Study 36-item Short-Form Health Survey, version 2, as well as showing their capacity to discriminate disease severity. Conclusions: The Spanish-language version of the CAMPHOR developed for use in Colombia was the result of a translation and cultural adaptation process that allows us to consider it equivalent to the original version, having shown good psychometric properties in the study sample. Therefore, its use to assess the impact of interventions on the HRQoL of patients with PAH or CTEPH is recommended, in research and clinical practice.

Keywords: Quality of life; Hypertension, pulmonary; Pulmonary embolism; Psychometrics.

Severe pulmonary hypertension is a debilitating disease with short life expectancy that often affects young people. Pleuropulmonary complications of systemic lupus erythematosus occur in 50-70% of patients. Severe symptomatic pulmonary hypertension in systemic lupus erythematosus is rare and carries a bad prognosis because a fatal outcome can occur within months. The authors describe, for the first time, a patient with systemic lupus erythematosus with severe pulmonary hypertension and secondary antiphospholipid syndrome who responded favorably to oral sildenafil, after unsuccessful use of prednisone, intravenous cyclophosphamide, warfarin and diltiazem.

Keywords: Vasodilator agents/therapeutic use. Lupus erythematosuos systemic. Antiphospholipid antibodies. Phosphodiesterase inhibitors.

Schistosomiasis mansoni is the third most prevalent endemic parasitic disease in the world. It is estimated that over 200 million people are infected with parasites belonging to one of the Schistosoma species. Of those, 270,000 people (4.6%) suffer from pulmonary arterial hypertension, which is associated with the hepatosplenic form of the disease. This high prevalence makes schistosomiasis-associated pulmonary hypertension the leading cause of pulmonary hypertension worldwide. However, no specific treatment for the pulmonary vascular component of the disease has yet been devised. We report the case of a patient with schistosomiasis-associated pulmonary hypertension who was treated satisfactorily with a phosphodiesterase-5 inhibitor (sildenafil).

Keywords: Schistosomiasis mansoni; Hypertension, pulmonary; Drug therapy.

Objective: Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods: Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results: The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion: In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Keywords: Drug tolerance; Expanded access program; Interstitial lung disease; Tyrosine kinase inhibitor.

Pulmonary hypertension is a common complication of sickle cell anemia. Despite the fact that the elevations in pulmonary artery pressures are slight, morbidity and mortality are high. In adult sickle cell anemia patients, pulmonary hypertension is emerging as a major risk factor for death. The pathogenesis of sickle cell anemia-related pulmonary hypertension is multifactorial, including hemolysis, impaired nitric oxide bioavailability, chronic hypoxemia, thromboembolism, chronic liver disease and asplenia. In the majority of patients, pulmonary arterial hypertension is the main cause of elevated pulmonary artery pressures. However, pulmonary venous hypertension also plays a role in a subgroup of patients. Specific data on the effects of treatment modalities for pulmonary hypertension in patients with sickle cell anemia are scarce. It is likely that all patients would benefit from maximization of sickle cell anemia therapy, and that patients with the severe form of the disease would benefit from treatment with selective pulmonary vasodilators and antiproliferative agents. Large trials evaluating the effects of treatment for pulmonary hypertension in the sickle cell anemia population are underway.

Keywords: Anemia, Sickle cell; Hemolysis; Hypertension, pulmonary; Nitric oxide.

Recent studies have suggested an association between pulmonary arterial hypertension (PAH) and thyroid diseases (hypothyroidism and hyperthyroidism). This combination has a good prognosis, because the increase in the pulmonary artery pressure is usually slight and reverses after the treatment of the thyroid disease. Although the exact mechanism involved in the pathogenesis of this combination has not yet been established, it has been hypothesized that thyroid hormones and autoimmunity have a direct influence. Due to the high prevalence of thyroid disease in patients with PAH, thyroid function tests should be considered in the investigation of every patient with PAH. In this review, we describe the prevalence of PAH in patients with thyroid diseases and the prevalence of thyroid disease in patients with PAH, as well as addressing the principal effects that thyroid diseases have on the respiratory system. In addition, we report the treatment effects in patients with these diseases.

Keywords: Hypertension, pulmonary; Graves disease; Hyperthyroidism; Hypothyroidism; Thyroid hormones; Echocardiography.

Background: The nucleoside adenosine is a potent vasodilator. Although its effect on the pulmonary arteries is well known, its influence on capillaries and veins has yet to be described. Objective: To evaluate the pre- and post-administration effects of adenosine on arterial and venous resistance in the pulmonary circulation of patients with primary pulmonary hypertension. Method: The study involved 7 patients with primary pulmonary hypertension and presenting a positive response to adenosine on the acute test. Before and after adenosine administration, arterial and venous resistances were determined by estimating pulmonary capillary pressure through analysis of pulmonary artery pressure decay curves. Results: Following adenosine administration, there was an increase in the cardiac index (from 1.71 ± 0.23 to 2.72 ± 0.74 L/min-1/m-2) and a decrease in pulmonary vascular resistance (from 2924 ± 1060 to 1975 ± 764 dynes/s/cm-5/m-2) with no significant variations in mean pulmonary artery pressure (pre: 75.6 ± 16.8 mmHg; post: 78.1 ± 18.8 mmHg), pulmonary wedge pressure (pre: 15.3 ± 1.5 mmHg; post: 15.4 ± 1.9 mmHg) and pulmonary capillary pressure (pre: 43.8 ± 5.8 mmHg; post: 44.5 ± 4.9 mmHg). The ratio between arterial resistance and total pulmonary vascular resistance also presented a less than significant variation (pre: 50 ± 15%; post: 49 ± 17%). These findings suggest that adenosine affects the capillaries and veins as well as the arteries. Conclusion: We can conclude that the adenosine mechanism is not restricted to the arterial aspect of the pulmonary circulation, and that analysis of pulmonary capillary pressure could prove useful in the study of various drugs that affect the pulmonary circulation.

Keywords: Key Words: Adenosine/pharmacocinetic. Adenosine/uso terapêutico. Blood pressure. Hypertension pulmonary.