The objective of this paper is to report some clinical and therapeutic aspects of inhaled nitric oxide in pediatrics. Some references were obtained from Medline® using the keywords: inhaled nitric oxide and pediatrics, and critical care. Other sources were the University library and personal files. Along the last decade, clinical trials with inhaled nitric oxide demonstrated only a few specific areas of proven efficacy and a variety of possible adverse events. Toxicity related to inhaled nitric oxide included metahemoglobinemia, cytotoxic pulmonary effects, excess production of nitrogen dioxide and peroxynitrite, and injury to the pulmonary surfactant system. The administration of inhaled nitric oxide to patients with severe left ventricular dysfunction and pulmonary hypertension should be cautious, since vasodilatation may increase pulmonary blood flow and lead to excessive preload. Some studies showed the clinical effects related to abrupt nitric oxide withdrawal, including rebound pulmonary hypertension. Current literature supports the therapeutic use of inhaled nitric oxide in persistent pulmonary hypertension of the newborn (gestational age ³ 34 weeks) to improve oxygenation and avoid extracorporeal oxygenation; and in congenital cardiopathy accompanied by pulmonary hypertension, especially in the immediate postoperative period. To date, research in pediatrics and multicentre trials in adults with inhaled nitric oxide therapy have failed to show mortality reduction or decrease the amount of time under mechanical ventilation for acute respiratory distress syndrome and acute lung injury. This indication needs further investigations. Persistent pulmonary hypertension is the most important indication for inhaled nitric oxide. The Food and Drug Administration has not approved inhaled nitric oxide in acute respiratory distress syndrome for adults and children.

Keywords: Nitric oxide/therapeutic use. Pediatrics. Pulmonary hypertension. Critical care.

This paper reviews in brief the role of nitric oxide in the respiratory physiology and in the pathology of some pulmonary diseases. The potential diagnostic and monitoring uses in several clinical situations are also discussed.

Keywords: respiratory tract diseases; lung diseases, obstructive; asthma; smoking; cystic fibrosis; bronchiectasis lung; lung transplantation

Nitric oxide (NO) is an endogenous vasoactive compound that contributes to pulmonary vascular homeostasis and is produced by three nitric oxide synthase (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS (eNOS)-all three of which are present in the lung. Studies using pharmacological inhibitors or knockout mice have shown that eNOS-derived NO plays an important role in modulating pulmonary vascular tone and attenuating pulmonary hypertension. However, studies focusing on the role of iNOS have shown that this isoform contributes to the pathophysiology of acute lung injury and acute respiratory distress syndrome. This review aimed at outlining the role played by NO in the control of pulmonary circulation, both under physiological and pathophysiological conditions. In addition, we review the evidence that the L-arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological target in the treatment of pulmonary vascular diseases.

Keywords: Nitric oxide; Arginine; Nitric oxide synthase; Cyclic GMP; Pulmonary circulation.

The aim of the study was to assess short-term repeatability of measurements of fractional exhaled nitric oxide (FENO) and its correlates in children in the 6- to 9-year age bracket participating in a respiratory epidemiological survey. FENO was measured in two sessions one week apart in 101 children. Participants were divided into three groups: asymptomatic (n = 76); symptomatic (n = 14); and asthma (n = 11). Absolute and relative differences between the measurements, as well as concordance correlation coefficients, were used in order to assess repeatability. The two FENO measurements were strongly correlated (0.98). Although intragroup comparisons of the two measurements were not significantly different (p = 0.2), intergroup comparisons were. FENO measurements are reproducible in children in epidemiological settings.

Keywords: Nitric oxide; Exhalation; Asthma.

The usefulness of serum tumor markers in lung cancer is not well defined. Objective: The aim of this study is to examine the correlation between serum tumor markers and tumor extension and its prognostic value. Patients and method: From February 1995 to September 1997, 103 patients with non-small cell lung carcinoma were evaluated at the Department of Thoracic Surgery. Serum levels of CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4, and NSE were determined before treatment. Results: The serum level of CYFRA21.1 was the most frequent elevated tumor marker (55%). Patients with advanced tumor had higher mean serum level of CEA (90.8 ng/ml), CYFRA21.1 (20.3 ng/ml) and CA15.3 (56.5%) than those with localized carcinoma, respectively 10.2 ng/ml, 12.6 ng/ml and 22.2 ng/ml. Considering all serum tumor markers evaluated in this study, only patients with elevated CEA had greater chance (5.6) of presenting with advanced non-small lung carcinoma than patients with normal CEA. Overall survival was influenced by performance status (p = 0.001), tumor extension (p = 0.006), elevated serum level of CEA (p = 0.043), more than two elevated serum tumor markers (p < 0.001), and type of treatment (p < 0.001). The prognostic value of anatomical tumor extension reached the limit of significance (p = 0.052); however, two or more elevated serum tumor markers and type of treatment had independent prognostic value (respectively, p = 0.035 and p = 0.005). Conclusion: None of these serum tumor markers had clinical value in the management of NSCLC patients.

Keywords: biological tumor markers, neoplasm staging, non-small cell lung carcinoma, prognosis

Objective: To investigate the clinical application of CT and CT-guided percutaneous transthoracic needle biopsy (CT-PTNB) in patients with indeterminate pulmonary nodules (IPNs). Methods: We retrospectively studied 113 patients with PNs undergoing CT and CT-PTNB. Variables such as gender, age at diagnosis, smoking status, CT findings, and CT-PTNB techniques were analyzed. Data analysis was performed with the Student's t-test for independent samples the chi-square test, and normal approximation test for comparison of two proportions. Results: Of the 113 patients studied, 68 (60.2%) were male and 78 (69%) were smokers. The diameter of malignant lesions ranged from 2.6 cm to 10.0 cm. Most of the IPNs (85%) were located in the peripheral region. The biopsied IPNs were found to be malignant in 88 patients (77.8%) and benign in 25 (22.2%). Adenocarcinoma was the most common malignant tumor, affecting older patients. The IPN diameter was significantly greater in patients with malignant PNs than in those with benign IPNs (p < 0.001). Having regular contour correlated significantly with an IPN being benign (p = 0.022), whereas spiculated IPNs and bosselated IPNs were more often malignant (in 50.7% and 28.7%, respectively). Homogeneous attenuation and necrosis were more common in patients with malignant lesions (51.9% and 26.9%, respectively) Conclusions: In our sample, CT and CT-PTNB were useful in distinguishing between malignant and benign IPNs. Advanced age and smoking were significantly associated with malignancy. Certain CT findings related to IPNs (larger diameter, spiculated borders, homogeneous attenuation, and necrosis) were associated with malignancy.

Keywords: Solitary pulmonary nodule; Tomography; Image-guided biopsy.

Nonadherence to inhaled corticosteroid therapy is common and has a negative effect on clinical control, as well as increasing morbidity rates, mortality rates and health care costs. This review was conducted using direct searches, together with the following sources: Medline; HighWire; and the Latin American and Caribbean Health Sciences Literature database. Searches included articles published between 1992 and 2008. The following methods of assessing adherence, listed in ascending order by degree of objectivity, were identified: patient or family reports; clinical judgment; weighing/dispensing of medication, electronic medication monitoring; and (rarely) biochemical analysis. Adherence rates ranged from 30 to 70%. It is recognized that the degree of adherence determined by patient/family reports or by clinical judgment is exaggerated in comparison with that obtained using electronic medication monitors. Physicians should bear in mind that true adherence rates are lower than those reported by patients, and this should be considered in cases of poor clinical control. Weighing the spray quantifies the medication and infers adherence. However, there can be deliberate emptying of inhalers and medication sharing. Pharmacies provide the dates on which the medication was dispensed and refilled. This strategy is valid and should be used in Brazil. The use of electronic medication monitors, which provide the date and time of each triggering of the medication device, although costly, is the most accurate method of assessing adherence. The results obtained with such monitors demonstrate that adherence was lower than expected. Physicians should improve their knowledge on patient adherence and use accurate methods of assessing such adherence.

Keywords: Patient compliance; Asthma/therapy; Asthma/prevention & control.

Objective: To evaluate the effectiveness and onset of action of formoterol delivered by dry-powder inhaler in reversing methacholine-induced bronchoconstriction. Methods: Patients presenting a drop in forced expiratory volume in one second > 20% after methacholine inhalation were included. A total of 84 patients were evaluated. All of the participating patients presented respiratory symptoms of unknown origin, which were being investigated. The patients were randomized to receive 200 µg of spray fenoterol (n = 41) or 12 µg of dry-powder inhaler formoterol (n = 43), both administered in order to achieve immediate reversal of methacholine-induced bronchoconstriction. We evaluated the decrease in forced expiratory volume in one second (in relation to the baseline value) after methacholine challenge and the dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second, as well as the increase in forced expiratory volume in one second (in relation to the baseline value) at five and ten minutes after bronchodilator use. Results: There were no significant differences related to gender, age, weight, height or dose of methacholine required to provoke a drop of 20% in forced expiratory volume in one second. Nor were there any significant differences in terms of baseline or post-methacholine forced expiratory volume in one second. In the fenoterol group, the mean postbronchodilator increase in forced expiratory volume in one second increase was 34% (at five minutes) and 50.1% (at ten minutes), compared with 46.5% (at five minutes) and 53.2% (at ten minutes) in the formoterol group. Conclusion: The bronchodilator effect of formoterol at five and ten minutes after methacholine-induced bronchoconstriction was similar to that of fenoterol. Despite being a long-acting bronchodilator, formoterol also has a rapid onset of action, which suggests that it could be employed as a relief medication in cases of bronchoconstriction occurring during asthma attacks.

Keywords: Asthma; Formoterol; Fenoterol; Inhalation therapy; Bronchodilation, Methacoline

This is a review of the medical literature regarding inhaled corticosteroids and their effects on growth and adrenal suppression in children and adolescents. A review of the literature, principally that published over the last five years, was conducted using Medline and searching indexes of articles published in national and international scientific journals. There is considerable controversy regarding the side effects of inhaled corticosteroids. In 21 studies evaluating the effect that inhaled corticosteroids have on growth, a statistically significant reduction (growth retarded by 1-1.5 cm) was observed within the first year of treatment with Beclomethasone or Budesonide inhalers. However, in studies of longer duration, no significant difference was found between final adult height and adult height of the parents. However, in ten studies of the use of inhaled corticosteroids and their effect on adrenal suppression, hypoglycemia and arrested development (no height or weight gains), as well as changes in morning serum levels and 24-h urinary levels of cortisol, were reported, especially when high doses of inhaled corticosteroids were used. Inhaled corticosteroids can reduce growth during the first year of use but do not affect adult height. However, further long-term studies are needed in order to determine the full impact of inhaled corticosteroids on final adult height. Height measures are a means of evaluating the safety and efficacy of the use of inhaled corticosteroids in children. Tests that evaluate the hypothalamic-pituitary-adrenal axis and adrenal insufficiency should be correlated with clinical symptoms and side effects.

The surgical treatment of patients with tracheobronchial stenosis requires individualized attention due to the complexity of its origin though tracheoplasty is considered to be the ideal procedure. The most common causes of stenosis are tracheal intubation and the development of neoplasias. These are the very conditions that most benefit from endoscopic treatment when surgical correction is not indicated. Today, endoscopic procedures include the application of different kinds of laser and dilators usually delivered with a rigid bronchoscope, as well as radiotherapy and stents that may be used separately or associated. Basically, there are two types of stents, metal or silicone. The metallic ones are more frequently indicated in cases of tracheomalacia and extrinsic compressive stenosis. Silicone are more applicable in cases of tracheobronchial obstruction resultant from acute inflammation or endoluminal tumor. Although these methods can be used interchangeably in some cases, the best way to correct tracheobronchial stenosis is to correctly decide upon the treatment as early as the preliminary steps.

Keywords: Tracheal stenosis. Orthopedics fixation devices. Angioplasty.

Objective: To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF) and whether pulmonary deposition correlates with disease severity or genotype. Methods: A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aeruginosa. Exclusion criteria were pulmonary exacerbation, changes in therapy between the study phases and FEV1 < 25%. All patients were submitted to pulmonary scintigraphy by means of a scintillation camera equipped with a low-energy all-purpose collimator in order to evaluate drug penetration following the administration of inhaled 99mTc-tobramycin, as well as to pulmonary perfusion with 99mTc-macroaggregated albumin (phase 1). One month later, the same procedure was performed following respiratory therapy and administration of inhaled albuterol (phase 2). Results: We included 24 patients (12 males) aged 5-27 years (mean ± SD: 12.85 ± 6.64 years). The Shwachman score (SS) was excellent/good in 8 patients, moderate/fair in 16 and poor in 0. Genotyping revealed that 7 patients were ΔF508 homozygotes, 13 were ΔF508 heterozygotes; and 4 presented other mutations. In all patients, lung deposition of tobramycin decreased in phase 2, especially in those with moderate/fair SS (p = 0.017) and in heterozygotes (p = 0.043). Conclusions: The use of a respiratory therapy technique and the administration of inhaled albuterol immediately prior to the use of inhaled tobramycin decreased the pulmonary deposition of the latter in CF patients, and this reduction correlates with disease severity and genotype.

Keywords: Cystic fibrosis; Tobramycin; Respiratory therapy; Albuterol; Radionuclide imaging.

Objective: To evaluate treatment compliance and use of inhaled medications of patients with asthma receiving complementary pharmaceutical care. Methods: A controlled prospective parallel study involving a study group and a control group. We selected 60 patients with persistent asthma and using metered-dose inhalers (MDIs), dry powder inhalers (DPIs) or both. The patients were evaluated three times over 60 days. Instructions were provided to the patients in the study group at all visits but only at the first visit to those in the control group. The patients using < 80% or > 120% of the total number of prescribed doses were classified as noncompliant. The inhalation technique was quantified by a scoring system. A satisfactory technique was defined as a score higher than 7 (maximum, 9) for MDIs and higher than 4 (maximum, 5) for DPIs. Results: The final study sample comprised 28 study group patients and 27 control group patients, of whom 18 (64.3%) and 20 (74.7%), respectively, were considered treatment compliant. From the first to the third visits, there were increases, in the study and control groups, in the median MDI-use score (from 3 [range, 0-5] to 8 [range, 8-9]; p < 0.001; and from 5 [range, 2-6] to 7 [range, 6-8]), as well as in the median DPI-use score (from 3 [range, 2-4] to 5 [range, 4-5] and from 3 [range, 2-4] to 4 [range, 3-5]). Conclusions: The counseling provided by the pharmacist to the patient was important to assist in the implementation of the appropriate inhalation technique, especially for MDI use.

Keywords: Asthma; Pharmaceutical services; Administration, inhalation;Metered dose inhalers; Medication adherence.

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.

Small animal models are particularly suitable for lung preservation studies, because they are simple and cost-effective. This brief communication focuses on the technical description of an ex vivo lung perfusion model in rats by means of a commercially available apparatus, which was the first to be installed in a thoracic surgery research laboratory in Brazil. The model and its preparation, together with its applications for lung preservation studies, are described in detail. All technical details can also be seen in a video posted on the website of the Brazilian Journal of Pulmonology.

Keywords: Lung transplantation; Reperfusion injury; Rats; Models, animal.

Objective: To develop a set of descriptive terms applied to the sensation of dyspnea (dyspnea descriptors) for use in Brazil and to investigate the usefulness of these descriptors in four distinct clinical conditions that can be accompanied by dyspnea. Methods: We collected 111 dyspnea descriptors from 67 patients and 10 health professionals. These descriptors were analyzed and reduced to 15 based on their frequency of use, similarity of meaning, and potential pathophysiological value. Those 15 descriptors were applied in 50 asthma patients, 50 COPD patients, 30 patients with heart failure, and 50 patients with class II or III obesity. The three best descriptors, as selected by the patients, were studied by cluster analysis. Potential associations between the identified clusters and the four clinical conditions were also investigated. Results: The use of this set of descriptors led to a solution with seven clusters, designated sufoco (suffocating), aperto (tight), rápido (rapid), fadiga (fatigue), abafado (stuffy), trabalho/inspiração (work/inhalation), and falta de ar (shortness of breath). Overlapping of descriptors was quite common among the patients, regardless of their clinical condition. Asthma was significantly associated with the sufoco and trabalho/inspiração clusters, whereas COPD and heart failure were associated with the sufoco, trabalho/inspiração, and falta de ar clusters. Obesity was associated only with the falta de ar cluster. Conclusions: In Brazil, patients who are accustomed to perceiving dyspnea employ various descriptors in order to describe the symptom, and these descriptors can be grouped into similar clusters. In our study sample, such clusters showed no usefulness in differentiating among the four clinical conditions evaluated.

Keywords: Dyspnea; Pulmonary disease, chronic obstructive; Asthma; Heart failure.

Background: Empyema is a serious disease classically characterized by purulence within the pleural cavity. Early diagnosis demands immediate treatment, although there is still great controversy surrounding the question of what is the best therapy. Objective: To analyze the method of using thoracentesis and pleural irrigation, combined with the intrapleural application of an antimicrobial agent, to treat empyema - and to compare this method with others described in the literature. Method: Between January 1999 and May 2000, 17 patients diagnosed with loculated or diffuse pleural empyema were submitted to thoracentesis, followed by thorough washing of the pleural cavity with isotonic solution and intrapleural administration of a non-irritating antimicrobial agent to the pleura. Results: The group of patients studied consisted of 15 men and 2 women, and the average age was 44. The most common clinical symptoms were fever, productive cough, chest pain and dyspnea, and the most common cause was pneumonia. Macroscopically, 12 patients presented obviously purulent pleural fluid. In 4 (26.67%) of the patients, the etiological agent was identified, the most frequent being Staphylococcus sp. Pulmonary decortication was indicated in 2 cases, and those 2 patients were therefore excluded. The average length of hospitalization was 17.1 days, although 3 patients received the treatment as outpatients. No recurrence or mortality was observed with the use of this methodology. Conclusion: This approach reduced the need for invasive procedures, proving to be safe and efficient, with lower rates of morbidity and mortality than other modalities of treatment.

Keywords: Empyema/Pleural, Pleura/Blood Supply, Treatment Outcome, Treatment Effectiveness.

We present a protocol to test a new surgical procedure for the treatment of patients with diffuse lung emphysema who, after having received the golden standard treatment (pulmonary rehabilitation), continue to present respiratory failure with disabling dyspnea. Ten patients with severe lung hyperinflation will be evaluated. The method proposed is designed to create alternative expiratory passages for air trapped in the emphysematous lung by draining the lung parenchyma, thereby establishing communication between the alveoli and the external environment. The ten patients selected will be required to meet the inclusion criteria and to give written informed consent. Those ten patients will be included in the study pending the approval of the Ethics in Research Committee of the São Paulo Santa Casa School of Medicine, São Paulo, Brazil. The protocol we will employ in order to evaluate the proposed procedure is feasible and will show whether debilitated patients suffering from diffuse pulmonary emphysema can benefit from this procedure, which could represent an alternative to lung transplant or lung volume reduction surgery, the only options currently available.

Keywords: Pulmonary emphysema; Pulmonary disease, chronic obstructive; Lung, hyperlucent.