Chronic dyspnea has a wide range of causes. The aim of the authors was to evaluate a diagnostic approach applied to patients with unexplained chronic (> 30 days) dyspnea, or when multiple causes were present. Methods: An algorithm for the work-up was applied: 1) complete history and physical examination; 2) bronchoprovocation test (BPT) and serial measurements of echocardiography; 3) cardiopulmonary exercise testing (CPET) and doppler echocardiography; 4) special tests: FRCT, V/Q scan, DCO, lung volumes, MIP, and others, as indicated. Results: Ninety patients were included, mean age of 51 ± 16 yr. Hyperventilation symptoms were present in 48, but associated with BHR or asthma in 19. Obstructive defect was present in 24 (asthma, 11; COPD, 8). Reduced FVC with normal FEV1/FVC was found in 10; explanations were asthma in 4, heart disease in 4. BPT was performed in 71 and was verified to be normal in 20; PEF variation was evaluated in 71, and was abnormal in 28, isolated in 16, and in 7 with asthma as final diagnosis. Echocardiography was performed in 44, and showed diastolic dysfunction in 11 out of 16 patients with final diagnosis of heart disease. CPET showed cardiovascular limitation in 19, hyperventilation in 19, and ventilatory defect in 12. CPET was decisive in 33 (38%), specially for heart diseases and to exclude causes suspected by clinical data. Respiratory disease was the explanation for dyspnea in 51 (59%): asthma (31), BHR (8), COPD (8), interstitial lung disease (4); other causes found were: heart disease (16), primary hyperventilation syndrome (8), obesity (5), neuromuscular disease (6), psychogenic dyspnea (2), and others (7). Multiple causes were found in 13 patients. Eight patients had non-recognizable etiology. Conclusion: An algorithm approach to chronic dyspnea resulted in diagnosis of 91% of the cases; spirometry, tests for BHR including PEF measurements, echocardiography, and CPET are essential for the investigation.

Keywords: Chronic dyspnea. Exercise test. Spirometry. Respiratory function tests. Bronchoprovocation tests. Peak expiratory flow. Echocardiography. Chest X-ray. Heart failure, congestive.

Chronic unexplained dyspnea and exercise intolerance represent common, distressing symptoms in outpatients. Clinical history taking and physical examination are the mainstays for diagnostic evaluation. However, the cause of dyspnea may remain elusive even after comprehensive diagnostic evaluation-basic laboratory analyses; chest imaging; pulmonary function testing; and cardiac testing. At that point (and frequently before), patients are usually referred to a pulmonologist, who is expected to be the main physician to solve this conundrum. In this context, cardiopulmonary exercise testing (CPET), to assess physiological and sensory responses from rest to peak exercise, provides a unique opportunity to unmask the mechanisms of the underlying dyspnea and their interactions with a broad spectrum of disorders. However, CPET is underused in clinical practice, possibly due to operational issues (equipment costs, limited availability, and poor remuneration) and limited medical education regarding the method. To counter the latter shortcoming, we aspire to provide a pragmatic strategy for interpreting CPET results. Clustering findings of exercise response allows the characterization of patterns that permit the clinician to narrow the list of possible diagnoses rather than pinpointing a specific etiology. We present a proposal for a diagnostic workup and some illustrative cases assessed by CPET. Given that airway hyperresponsiveness and pulmonary vascular disorders, which are within the purview of pulmonology, are common causes of chronic unexplained dyspnea, we also aim to describe the role of bronchial challenge tests and the diagnostic reasoning for investigating the pulmonary circulation in this context.

Keywords: Dyspnea; Exercise test; Bronchial provocation tests; Vascular diseases.

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.

Objective: To determine the prevalence of factors associated with difficult-to-control asthma. Methods: Patients with severe asthma were selected from the outpatient asthma clinic of the Ribeirão Preto School of Medicine Hospital das Clínicas. The patients were divided into two groups: controlled severe asthma and difficult-to-control severe asthma. After new attempts to optimize the severe asthma treatment, a questionnaire was applied, and additional tests for factors associated with difficult-to-control asthma, such as environmental and occupational exposure, smoking history, social factors, rhinitis/sinusitis, gastroesophageal reflux disease (GERD), obstructive sleep apnea, congestive heart failure (CHF), pulmonary embolism, cystic fibrosis, vocal cord dysfunction, α-1 antitrypsin deficiency, and Churg-Strauss syndrome, were performed. Results: 77 patients with severe asthma were selected, of which 47 suffered from hard-to-control asthma, being 68.1% female, with mean age of 44.4 years (±14.4), and forced expiratory volume in one second of 54.7% (±18.3). The most factors most often associated with difficult-to-control asthma were noncompliance with treatment (68%), rhinitis/sinusitis (57%), GERD (49%), environmental exposure (34%), occupational exposure (17%), smoking history (10%), obstructive sleep apnea (2%), and CHF (2%). At least one of these factors was identified in every case. Conclusions: Noncompliance with treatment was the factor most often associated with difficult-to-control asthma, underscoring the need to investigate comorbidities in the evaluation of patients with this form of the disease.

Keywords: Asthma; Smoking; Gastroesophageal reflux; Patient compliance; Rhinitis; Sinusitis.

Abstract Objective: To determine the validity and reproducibility of two subjective instruments to assess limitations in activities of daily living (ADLs) in patients with chronic obstructive pulmonary disease (COPD) in Brazil: the Pulmonary Functional Status and Dyspnea ­Questionnaire ‑ ­Modified version (PFSDQ-M) and the Medical Research Council (MRC) scale. Methods: Thirty patients with COPD (age, 67 ± 10 years; males, 17; forced expiratory volume in one second, 42% ± 13% of predicted) completed the Portuguese-language versions of the two instruments on two occasions, one week apart. The PFSDQ-M has three components: influence of dyspnea on ADLs, influence of fatigue on ADLs and change experienced by the patient with ADLs. The MRC scale is simple, with only five items, in which patients report the degree to which dyspnea limits their performance of ADLs. The traditional Saint George's Respiratory Questionnaire (SGRQ), previously validated for use in Brazil, was used as a validation criterion. Results: The test-retest reliability (intraclass correlation coefficient) of the PFSDQ-M was 0.93, 0.92 and 0.90 for the dyspnea, fatigue and change components, respectively, compared with 0.83 for the MRC scale. Bland-Altman plots showed good test-retest concordance for the PFSDQ-M. The components of the PFSDQ-M and the MRC scale correlated significantly with all of the domains and the total score on the SGRQ (0.49 < r < 0.80; p < 0.01 for all). Conclusions: The Portuguese-language versions of the PFSDQ-M and the MRC scale proved reproducible and valid for use in patients with COPD in Brazil.

Keywords: Pulmonary disease, chronic obstructive; Activities of daily living; Validation studies.

Imaging the airways has always been a difficult task. Since the introduction of high resolution computed tomography a lot has been achieved in this area, specially in the visualization of the small airways. With the fine details provided by this technique, morphological changes related to the bronchioles can now be detected in a way hitherto impossible. This study was aimed at the description of the CT scan signs of airway disease that were present in a group of 36 patients suffering from chronic respiratory symptoms of cough and great amount of sputum production (bronchial suppuration) attending the outpatient clinics of the Pulmonary Disease Service of the State University of Campinas School of Medicine. Among these patients, 12 were diagnosed as having cystic fibrosis, and 24, other diseases with chronic sputum production. The authors looked for the direct signs of airway disease, such as thickening of the wall and dilatation of the lumen of large airways and these same abnormalities, appearing as micronodules at the center of the lobule and branching linear opacities, or a combination of the two (the so-called "tree in bud" pattern), when the disease is predominantly located in the small airways, in the films obtained from all the patients. The indirect signs of small airway disease, like mosaic perfusion and air-trapping, were also analyzed. Imaging of the airways has come of age with the use of high-resolution computed tomography and there is little doubt that this technique is now the most sensitive radiographic method for imaging the small airways, this previously hidden area of the lungs.

Keywords: Computed tomography. High resolution computed tomography. Airway diseases. Bronchiolar diseases. Bronchiectasis.

Objective: To determine the prevalence of atopy and to evaluate clinical, laboratory, and radiological profiles in patients with COPD. Methods: This was a cross-sectional study involving outpatients with stable COPD (defined by the clinical history and a post-bronchodilator FEV1/FVC < 70% of the predicted value). The patients completed a questionnaire regarding clinical characteristics and atopy, after which they underwent nasal lavage cytology, skin prick testing, chest X-rays, arterial blood gas analyses, and determination of total serum IgE. Results: Of the 149 subjects studied, 53 (35.6%), 49 (32.8%), and 88 (59.1%) presented with nasal eosinophilia, a positive skin prick test result, and symptoms of allergic rhinitis, respectively. Correspondence analysis confirmed these findings, showing two distinct patterns of disease expression: atopy in patients with COPD that was less severe; and no evidence of atopy in those with COPD that was more severe (reduced FEV1 and hyperinflation). There was a statistically significant association between nasal eosinophilia and a positive bronchodilator response. Conclusions: Using simple and reproducible methods, we were able to show that there is a high frequency of atopy in patients with COPD. Monitoring inflammation in the upper airways can be a useful tool for evaluating respiratory diseases in the elderly and in those with concomitant asthma and COPD, a clinical entity not yet fully understood.

Keywords: Pulmonary disease, chronic obstructive; Allergy and immunology; Nasal lavage fluid; Asthma; Rhinitis, allergic, perennial.

Macrophage activation syndrome is a rare and potentially life-threatening disease. It occurs due to immune dysregulation manifested as excessive macrophage proliferation, typically causing hepatosplenomegaly, pancytopenia and hepatic dysfunction. Here, we report an unusual case of macrophage activation syndrome presenting as dyspnea, as well as (reported here for the first time) high resolution computed tomography findings of an excavated nodule, diffuse ground glass opacities and consolidations (mimicking severe pneumonia or alveolar hemorrhage). The patient was successfully treated with human immunoglobulin. We recommend that macrophage activation syndrome be considered in the differential diagnosis of respiratory failure. Rapid diagnosis and treatment are essential to achieving favorable outcomes in patients with this syndrome.

Keywords: Macrophage activation; Lymphohistiocytosis, hemophagocytic; Tomography, X-ray computed; Lung diseases, interstitial.

Objective: Assess the relationship between adherence to long-term oxygen therapy (LTOT) with mortality in patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure and their clinical features. Methods: Longitudinal retrospective analysis of 254 patients with COPD and chronic respiratory failure from 2008 to 2016. At baseline, we evaluated the diagnosis, spirometry values, arterial blood gas analysis, blood count, pulse oximetry, body composition and health questionnaires (dyspnea, quality of life, anxiety and depression). For referred adherence analysis to LTOT we included 199 patients, divided according to prescription of oxygen: 12h/day (G1), 15h/day (G2) and 24h/day (G3). The cause of death and dates were studied over the five-year period. Results: In five years we identified 124 deaths (62.3%). No significant difference was found in mortality between the adherence groups (p=0.75) nor did we find differences in the clinical parameters evaluated. LTOT prescription was not associated with mortality (p=0.07). In Cox regression analysis, there was no association between mortality and non-adherence to LTOT (HR: 0.75; IC95%: 0.21-2.70). The risk of mortality was increased in G3 compared with G1 (HR: 7.16; IC 95%: 1.44-35.38) and in those with a higher depression score (HR: 1.35; IC: 1.14-1.59). Conclusion: No association was found between LTOT adherence and mortality in patients with COPD and respiratory failure. There were no clinical differences between the adherence groups.

Keywords: Chronic obstructive pulmonary disease; Oxygen therapy; Cooperation and treatment adherence; Morbidity and mortality indicators.

Objective: To determine the proportion of asthma patients with a poor perception of dyspnea, correlating the level of that perception with the severity of acute bronchoconstriction, bronchial hyperresponsiveness, use of maintenance medication, and asthma control. Methods: Uncontrolled clinical trial involving asthma patients treated at the Pulmonology Outpatient Clinic of the São Lucas Hospital, in Porto Alegre, Brazil. Methacholine challenge testing was performed using a five-breath dosimeter protocol. The perception of dyspnea after each breath was determined using the Borg scale. Data concerning asthma control, medication in use, and use of rescue short-acting bronchodilators were recorded. Results: Of the 65 patients included in the study, 53 completed the evaluation. Of those, 32 (60.5%) showed adequate perception of dyspnea after the methacholine challenge test, whereas 21 (39.5%) did not perceive any changes in the degree of dyspnea even after a 20% fall in FEV1. There were no significant differences between the two groups regarding baseline FEV1, percentage fall in FEV1, and the dose of methacholine causing a 20% fall in FEV1. The perception of dyspnea was not significantly associated with age (p = 0.247); gender (p = 0.329); use of maintenance medication (p = 0.152); asthma control (p = 0.562), bronchial hyperresponsiveness (p = 0.082); or severity of acute bronchoconstriction (p = 0.749). Conclusions: A significant proportion of asthma patients have a poor perception of dyspnea. The factors related to the inability of these patients to identify changes in pulmonary function have not yet been well defined. In order to reduce asthma-related morbidity and mortality, it is essential that this group of patients be identified and counseled.

Keywords: Asthma; Dyspnea; Airway obstruction.

Objectives: To evaluate the incidence of venous thromboembolism (VTE) in hospitalized patients with COVID-19 who underwent diagnostic tests for suspected VTE, and to correlate the IMPROVE-DD score with the incidence of VTE in this cohort. Methods: This retrospective study included consecutive patients with COVID-19 and suspected VTE, admitted between March 2020 and September 2021 at a private hospital in Salvador (BA), Brazil, who underwent lower or upper limb venous Doppler ultrasound or chest angiotomography. Descriptive analyses and comparisons using the chi-square test were performed to identify factors potentially associated with the risk of VTE. Results: A total of 517 patients were included, with an in-hospital VTE incidence of 18.6% (96 events). Risk factors significantly associated with VTE included obesity, ICU admission, central venous catheter use, longer hospital stays, greater lung tomographic involvement/severity, the need for mechanical ventilation, D-dimer levels at least twice the upper limit of normal (2xULN), and the IMPROVE-DD score. The mean IMPROVE-DD score among patients with VTE was 4.7 (±3) versus 3.3 (±2.4) in those without VTE (p < 0.0001). D-dimer 2xULN was sensitive in identifying 94% of the 96 patients with VTE (p < 0.0001). The in-hospital mortality rate was 14.1%, with higher rates observed in patients with VTE (24%) compared to those without VTE (11.9%) (p = 0.003). Conclusions: The incidence of VTE in hospitalized COVID-19 patients was high and correlated with increased mortality. The IMPROVE-DD score effectively identified patients at risk for in-hospital VTE, suggesting it could help to identify a high-risk subgroup that may benefit from extended thromboprophylaxis.

Keywords: Venous thromboembolism, COVID-19, IMPROVE-DD.

Objective: To characterize a population of patients with bronchiectasis, correlating clinical, radiological, and functional aspects with the severity of dyspnea. Methods: This was a cross-sectional study involving adult patients with HRCT-confirmed bronchiectasis, categorized according to the severity of dyspnea (as being mildly or severely symptomatic, on the basis of the modified Medical Research Council scale). We correlated the severity of dyspnea with clinical parameters, functional parameters (spirometry values, lung volumes, and DLCO), and CT parameters. Results: We evaluated 114 patients, 47 (41%) of whom were men. The median age (interquartile range) was 42 years (30-55 years). The most common form was idiopathic bronchiectasis. Of the 114 patients, 20 (17.5%) were colonized with Pseudomonas aeruginosa and 59 (51.8%) were under continuous treatment with macrolides. When we applied the Exacerbation in the previous year, FEV1, Age, Colonization, Extension, and Dyspnea score, the severity of dyspnea was categorized as moderate in 54 patients (47.4%), whereas it was categorized as mild in 50 (43.9%) when we applied the Bronchiectasis Severity Index. The most common lung function pattern was one of obstruction, seen in 95 patients (83.3%), and air trapping was seen in 77 patients (68.7%). The prevalence of an obstructive pattern on spirometry was higher among the patients with dyspnea that was more severe, and most functional parameters showed reasonable accuracy in discriminating between levels of dyspnea severity. Conclusions: Patients with bronchiectasis and dyspnea that was more severe had greater functional impairment. The measurement of lung volumes complemented the spirometry data. Because bronchiectasis is a complex, heterogeneous condition, a single variable does not seem to be sufficient to provide an overall characterization of the clinical condition.

Keywords: Bronchiectasis; Dyspnea; Respiratory function tests; Multidetector computed tomography; Plethysmography.

Background: Dyspnea is a symptom that is difficult to evaluate, especially in occupational diseases. Objective: To evaluate the relationship between chronic dyspnea, in its varying degrees of severity, and the functional repercussions for dysfunction or incapacitation in former workers with asbestosis. Method: A total of 40 former workers diagnosed with asbestosis were evaluated. Dyspnea scores were determined using the modified Medical Research Council scale, the 1984 and 1993 American Medical Association scales, and the Baseline Dyspnea Index. Spirometry, measurement of diffusion capacity for carbon monoxide and cardiopulmonary exercise tests (incremental and submaximal) were also performed. Results: Based on scores obtained using the Medical Research Council and 1984 American Medical Association scales, respectively, 72.5% and 67.5% of the subjects were classified as dyspneic, compared with 37.5% and 31.6%, respectively, using the 1993 American Medical Association and Baseline Dyspnea Index scales. There was greater concordance between the Medical Research Council and 1993 American Medical Association scales, as well as between the 1984 and 1993 American Medical Association scales, when the categories of "absent" and "mild" were grouped. No significant relation was found between dyspnea, as determined by each of the scales, and functional abnormalities - either at rest or during exercise. Conclusion: In individuals with asbestosis, the degree of concordance among the available dyspnea scales varies significantly. There is a real need for dyspnea indices that evaluate respiratory dysfunction at rest and during exercise.

Keywords: Asbestosis/diagnosis. Dyspnea/physiopathology. Spirometry/methods.

Objective: To evaluate the understanding of asthma and the clinical improvement in patients with moderate or severe persistent asthma prior to and after their participation in an educational program presented during the routine outpatient visits. Methods: This was a prospective pilot study involving 164 patients over a two-year period. The educational program, presented to small groups on outpatient visit days, consisted of lectures divided into three parts: pathophysiology; environmental control; and treatment, including training in the inhalation technique. The program was evaluated using standardized questionnaires on clinical improvement and understanding of the disease. Results: By the end of the first year, 120 patients had completed three visits, and 51 of those patients were revaluated at the end of the second year. The mean age of the patients was 44 years, 70% were female, and 43% had up to eight years of schooling. The educational intervention significantly increased the understanding of the disease (p < 0.001), and allowed greater clinical improvement (p < 0.05) with a decrease in the use of oral corticosteroids, fewer visits to the emergency room and fewer days missed from work or school. Conclusions: The educational program offered during the routine outpatient visits of adult patients with asthma at our clinic resulted in a progressive long-term increase in knowledge, as well as in clinical improvement.

Keywords: Asthma; Adult; Patient education as topic.