Objective: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler) in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler). Methods: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. Results: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg, respectively, whereas it was 353.0 µg and 11.1 µg in the reference formulation. These values are within the recommended range for this type of formulation (75-125% of the labeled dose). The fine particle fraction (< 5 µm) for budesonide and formoterol was 45% and 56%, respectively, in the test formulation and 54% and 52%, respectively, in the reference formulation. Conclusions: For both of the formulations tested, the levels of active ingredients, dose uniformity, and aerodynamic diameters were suitable for use with the respective dry powder inhalers.

Keywords: : Asthma; Budesonide; Bronchodilator agents; Drug therapy, combination.

Objective: To measure peak inspiratory flow (PIF) and assess dynamic lung function in children and adolescents with asthma, as well as to determine the association of PIF with dynamic lung function and clinical variables. Methods: This was a cross-sectional study of children and adolescents with asthma using dry powder inhalers (DPIs) regularly. The control group included sex-, age-, weight-, and height-matched individuals without lung disease. Socioeconomic and clinical variables were collected. PIF and dynamic lung function variables were obtained with a specific device. Between-group comparisons were made with the Student's t-test and ANOVA. Multiple linear regression analysis was performed, and Pearson's correlation coefficients were calculated to assess associations between PIF and the other variables. Results: A total of 88 individuals (44 asthma patients and 44 controls) participated in the study. PIF and respiratory muscle strength (S-index) values were lower in the asthma patients than in the controls. PIF correlated positively with age, weight, height, and S-index in the asthma group. After controlling for height, we found an increase of 0.05 units in PIF associated with an increase of 1 unit in the S-index in the asthma group. Conclusions: PIF appears to be lower in children and adolescents with asthma than in those without asthma, correlating positively with age, height, weight, and respiratory muscle strength.

Keywords: Dry powder inhalers; Asthma; Muscle strength; Child; Adolescent.

Objective: The aim of this study was to determine the factors associated with nocturnal, productive and dry cough among young adults in Nigeria. Methods: We evaluated 498 subjects, 20-44 years of age, in Ilorin, Nigeria, using the European Community Respiratory Health Survey (ECRHS) questionnaire, administered by trained interviewers. Results: Nocturnal cough was associated with asthma (OR = 10.87; p < 0.01), nasal allergy (OR = 6.33; p < 0.01), smoking (OR = 3.10; p < 0.01), skilled manual and non-manual work (OR = 2.86 and 2.10, respectively; p < 0.01 for both) and female gender (OR = 1.33; p = 0.17). Productive cough was associated with skilled manual and non-manual work (OR = 3.82 and 3.03, respectively; p < 0.01 for both), smoking (OR = 3.10; p < 0.01), asthma (OR = 3.27; p < 0.01) and nasal allergy (OR = 5.81; p < 0.01). Dry cough was associated with asthma (OR =5.18; p < 0.01) obesity (OR =1.88; p = 0.19), smoking (OR = 1.77; p = 1.44), nasal allergy (OR = 1.45; p = 0.26) and female gender (OR =1.36; p = 0.33). Age, gender, type of residence and obesity were not significantly associated with any type of cough (p > 0.05). Conclusions: Early prevention and treatment of conditions associated with cough, as well as the modification of social factors commonly associated with cough, are needed in order to reduce respiratory morbidity.

Keywords: Cough; Smoking; Asthma; Rhinitis; Nigeria.

To evaluate the characteristics of users of inhalers and the frequency of inhaler use among adolescents and adults with self-reported physician-diagnosed asthma, bronchitis, or emphysema. Methods: A population-based study conducted in the city of Pelotas, Brazil, involving 3,670 subjects ≥ 10 years of age, evaluated with a questionnaire. Results: Approximately 10% of the sample reported at least one of the respiratory diseases studied. Among those individuals, 59% reported respiratory symptoms in the last year, and, of those, only half reported using inhalers. The use of inhalers differed significantly by socioeconomic status (39% and 61% for the lowest and the highest, respectively, p = 0.01). The frequency of inhaler use did not differ by gender or age. Among the individuals reporting emphysema and inhaler use, the use of the bronchodilator-corticosteroid combination was more common than was that of a bronchodilator alone. Only among the individuals reporting physician-diagnosed asthma and current symptoms was the proportion of inhaler users higher than 50%. Conclusions: In our sample, inhalers were underutilized, and the type of medication used by the individuals who reported emphysema does not seem to be in accordance with the consensus recommendations.

Keywords: Metered dose inhalers; Asthma; Pulmonary disease, chronic obstructive; Bronchitis; Emphysema; Dry powder inhalers.

Objective: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma. Methods: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. Results: We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. Conclusions: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and safety, making it a new treatment option for persistent asthma. (ClinicalTrials.gov Identifier:NCT01202084 [http://www.clinicaltrials.gov/])

Keywords: Asthma; Steroids; Bronchodilator agents; Administration, inhalation.

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.

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

The clinical-radiographic presentation and tuberculosis prediction in patients that have undergone dry pleural biopsy, as well as its usefulness and complications, have been evaluated in this retrospective study, conducted in the Octávio Mangabeira Hospital (Salvador, Bahia, Brazil), where 107 patients consecutively submitted to this exam have been analyzed. Altogether 108 biopsies have been performed using Cope's needle (biopsies of both hemithoraxes were performed in one patient). The following diagnoses were obtained: a) tuberculosis (n = 66); b) probable tuberculosis (n = 4); c) neoplasm (n = 2); d) parapneumonic (n = 3), and e) not determined (32). Sixty-seven (62.6%) of the patients were male, and mean age was 34.5 ± 15.4 years. Analyses carried out compare patients diagnosed with tuberculosis (whether confirmed or probable) to those with different diagnoses (miscellaneous). Tuberculosis patients were younger (p < 0.01), expectoration was less frequent (p < 0.01), previous tuberculosis was less often reported (p = 0.04) and PPD reactivity was more frequent (p < 0.01). No significant differences were found between the two groups as to the extent of pleural commitment and its variation in the period observed. Presence of acinar infiltrations in the upper lobes was correlated with tuberculosis diagnosis in the 13 patients in which this feature was observed. Pleural fragments were present in 100 out of 108 cases (92.6%) and the diagnosis was made in the first biopsy in 64 out of 108 cases (59.3%). Ten minor complications have occurred (9.3%) in the 108 biopsies: 6 bloody sputums, 3 small pneumothoraxes, and one moderate subcutaneous emphysema. The authors conclude that for the various predictive indicators of tuberculosis analyzed, except for the presence of acinar infiltrations in the upper lobes, there is broad overlap between the two groups compared, meaning that a safe clinical diagnosis cannot be provided and thus reinforcing the need of performing biopsies. Dry pleural biopsy offers a satisfactory diagnostic yield in areas with high prevalence of tuberculosis and proved safe, when performed by experienced personnel.

Keywords: Pleural tuberculosis. Pleural thickening. Pleural biopsy. Diagnosis.

Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

Keywords: Tuberculosis, pulmonary, Drug combinations; Recurrence.

Objective: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL) of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. Methods: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. Results: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. Conclusions: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

Keywords: Carcinoma, non-small-cell lung; Quality of life; Palliative care; Carboplatin; Paclitaxel.

Objective: To identify incorrect inhaler techniques employed by patients with respiratory diseases in southern Brazil and to profile the individuals who make such errors. Methods: This was a population-based, cross-sectional study involving subjects ≥ 10 years of age using metered dose inhalers (MDIs) or dry powder inhalers (DPIs) in 1,722 households in the city of Pelotas, Brazil. Results: We included 110 subjects, who collectively used 94 MDIs and 49 DPIs. The most common errors in the use of MDIs and DPIs were not exhaling prior to inhalation (66% and 47%, respectively), not performing a breath-hold after inhalation (29% and 25%), and not shaking the MDI prior to use (21%). Individuals ≥ 60 years of age more often made such errors. Among the demonstrations of the use of MDIs and DPIs, at least one error was made in 72% and 51%, respectively. Overall, there were errors made in all steps in 11% of the demonstrations, whereas there were no errors made in 13%.Among the individuals who made at least one error, the proportion of those with a low level of education was significantly greater than was that of those with a higher level of education, for MDIs (85% vs. 60%; p = 0.018) and for DPIs (81% vs. 35%; p = 0.010).Conclusions: In this sample, the most common errors in the use of inhalers were not exhaling prior to inhalation, not performing a breath-hold after inhalation, and not shaking the MDI prior to use. Special attention should be given to education regarding inhaler techniques for patients of lower socioeconomic status and with less formal education, as well as for those of advanced age, because those populations are at a greater risk of committing errors in their use of inhalers.

Keywords: Asthma; Pulmonary disease, chronic obstructive; Dry powder inhalers; Metered dose inhalers.

Objective: To evaluate the use of inhaler devices by patients with severe asthma treated via the Programa para o Controle da Asma e Rinite Alérgica na Bahia (ProAR, Bahia State Asthma and Allergic Rhinitis Control Program), recording the frequency of their errors in performing key steps and the relationship between such errors and the lack of asthma control. Methods: A cross-sectional study involving 467 patients enrolled in the ProAR in the city of Salvador, Brazil. The devices evaluated were metered dose inhalers (MDIs), with or without a spacer, and dry powder inhalers (DPIs; Pulvinal® or Aerolizer®). For the assessment of the inhalation technique, a checklist was used; the patients were asked to demonstrate the technique so that an interviewer could observe all of the steps performed. For the assessment of asthma control, we used the 6-item asthma control questionnaire. Results: Most of the patients showed appropriate inhalation techniques when using the devices. When using an MDI, few patients made mistakes in the key step of "coordinating activation and inhalation" (5.2% and 9.1% with and without the use of a spacer, respectively). During Pulvinal® use, 39% of the patients did not inhale quickly and deeply, compared with only 5.8% during Aerolizer® use. Of the patients that made use of Aerolizer® alone, 71.3% appropriately performed all of the essential steps, and their asthma was controlled. Conclusions: Most of the patients in this sample, all of whom had been submitted to periodic checks of their inhalation technique (as part of the program), used the devices appropriately. Proper inhalation technique is associated with asthma symptom control.

Keywords: Asthma; Administration, inhalation; Metered dose inhalers; Dry powdered inhalers.

Objective: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. Methods: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). Results: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. Conclusions: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination.

Keywords: Pulmonary disease, chronic obstructive/epidemiology; Acute disease; Acute-phase proteins; Hospitalization; Patient readmission; Inflammation.

Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients.

Keywords: Administration, inhalation; Aerosols/administration & dosage; Asthma/prevention & control.

Objective: To compare the influence of two different ventilation strategies-volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV)-on the functional performance of lung grafts in a canine model of unilateral left lung transplantation using donor lungs harvested after three hours of normothermic cardiocirculatory arrest under mechanical ventilation. Methods: The study comprised 40 mongrel dogs, randomized into two groups: VCV and PCV. Of the 20 recipients, 5 did not survive the transplant, and 5 died before the end of the post-transplant assessment period. The remaining 10 survivors (5 in each group) were evaluated for 360 min after lung transplantation. The functional performance of the grafts was evaluated regarding respiratory mechanics, gas exchange, and lung graft histology. Results: There were no significant differences between the groups regarding respiratory mechanics (peak inspiratory pressure, plateau pressure, mean airway pressure, dynamic compliance, and static compliance) or gas exchange variables (PaO2, venous oxygen tension, PaCO2, venous carbon dioxide tension, and the arterial-venous oxygen content difference). The histopathological findings were consistent with nonspecific acute lung injury and did not differ between the groups. Conclusions: This model of lung transplantation showed that the functional performance of lung grafts was not influenced by the ventilation strategy employed during the first six hours after reperfusion.

Keywords: Pulmonary ventilation; Respiration, artificial; Lung transplantation; Dogs; Organ preservation.

We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF). Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right) lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation, the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.

Keywords: Idiopathic pulmonary fibrosis; Lung transplantation; Case reports [publication type].

Objective: To evaluate the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination, in comparison with budesonide alone, in patients with uncontrolled asthma. Methods: This was a randomized, double-blind, multicenter, phase III, parallel clinical trial, comparing the short-term efficacy and safety of the combination of budesonide (400 μg) and formoterol (12 μg), with those of budesonide alone (400 μg), both delivered via a dry powder inhaler, in 181 patients with uncontrolled asthma. The age of the patients ranged from 18 to 77 years. After a run-in period of 4 weeks, during which all of the patients received budesonide twice a day, they were randomized into one of the treatment groups. The treatment consisted of the administration of the medications twice a day for 12 weeks. The primary outcome measures were FEV1, FVC, and morning PEF. We performed an intention-to-treat analysis of the data. Results: In comparison with the budesonide-only group patients, those treated with the budesonide-formoterol combination showed a significant improvement in FEV1 (0.12 L vs. 0.02 L; p  =   0.0129) and morning PEF (30.2 L/min vs. 6.3 L/min; p  = 0.0004). These effects were accompanied by good tolerability and safety, as demonstrated by the low frequency of adverse events, only minor adverse events having occurred. Conclusions: The single-capsule combination of budesonide-formoterol appears to be efficacious and safe. Our results indicate that this formulation is a valid therapeutic option for obtaining and maintaining asthma control. (ClinicalTrials.gov Identifier: NCT01676987 [http://www.clinicaltrials.gov/])

Keywords: Asthma; Budesonide; Adrenergic beta-2 receptor agonists.

We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

Keywords: Lung; Granuloma, foreign-body; Cocaine-related disorders.