A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study.

Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.

European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

Quality standards for managing children and adolescents with bronchiectasis: an international consensus.

The global burden of bronchiectasis in children and adolescents is being recognised increasingly. However, marked inequity exists between, and within, settings and countries for resources and standards of care afforded to children and adolescents with bronchiectasis compared with those with other chronic lung diseases. The European Respiratory Society (ERS) clinical practice guideline for the management of bronchiectasis in children and adolescents was published recently. Here we present an international consensus of quality standards of care for children and adolescents with bronchiectasis based upon this guideline. The panel used a standardised approach that included a Delphi process with 201 respondents from the parents and patients' survey, and 299 physicians (across 54 countries) who care for children and adolescents with bronchiectasis. The seven quality standards of care statements developed by the panel address the current absence of quality standards for clinical care related to paediatric bronchiectasis. These internationally derived, clinician-, parent- and patient-informed, consensus-based quality standards statements can be used by parents and patients to access and advocate for quality care for their children and themselves, respectively. They can also be used by healthcare professionals to advocate for their patients, and by health services as a monitoring tool, to help optimise health outcomes.

CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia.

Evaluation of ciliary beat frequency (CBF) performed by high-speed videomicroscopy analysis (HVMA) is one of the techniques required for the correct diagnosis of primary ciliary dyskinesia (PCD). Currently, due to lack of open-source software, this technique is widely performed by visually counting the ciliary beatings per a given time-window. Our aim was to generate open-source, fast and intuitive software for evaluating CBF, validated in Portuguese PCD patients and healthy volunteers. Nasal brushings collected from 17 adult healthy volunteers and 34 PCD-referred subjects were recorded using HVMA. Evaluation of CBF was compared by two different methodologies: the new semi-automated computer software CiliarMove and the manual observation method using slow-motion movies. Clinical history, nasal nitric oxide and transmission electron microscopy were performed for diagnosis of PCD in the patient group. Genetic analysis was performed in a subset (n=8) of suspected PCD patients. The correlation coefficient between the two methods was R2=0.9895. The interval of CBF values obtained from the healthy control group (n=17) was 6.18-9.17 Hz at 25°C. In the PCD-excluded group (n=16), CBF ranged from 6.84 to 10.93 Hz and in the PCD group (n=18), CBF ranged from 0 to 14.30 Hz. We offer an automated open-source programme named CiliarMove, validated by the manual observation method in a healthy volunteer control group, a PCD-excluded group and a PCD-confirmed group. In our hands, comparisons between CBF intervals alone could discern between healthy and PCD groups in 78% of the cases.

Primary ciliary dyskinesia due to CCNO mutations-A genotype-phenotype correlation contribution.

Primary ciliary dyskinesia (PCD) is genetically and clinically heterogeneous. CCNO mutations are associated with chronic destructive lung disease and were first described in 2014. Early reports suggest that CCNO is mutated more frequently than expected, however, these are considered rare. We report on three eleven-year-old children with PCD due to CCNO mutations. All children presented early-onset respiratory symptoms, no cardiac or situs anomalies and moderate to severe clinical courses. Patients 1 and 3 were admitted to a neonatal intensive care unit due to respiratory distress. Patients 1 and 2 had atelectasis and lobar collapse, for which lobectomy was performed for patient 1. Patient 3 also presented otitis media with effusion with conductive hearing loss, requiring tympanostomy tube insertion twice. Diagnosis of PCD for all three required repeated nasal brushings, delaying diagnostic confirmation. Microscopy analysis revealed severely decreased numbers of cilia, but normal ultrastructure and uncoordinated beat pattern in the residual cilia. Surprisingly, the prevalence of pathogenic CCNO variants in our centre is higher than expected (three out of sixteen patients). Pathogenic variants in PCD-causing genes lead to specific ultrastructural defects, and there is a suggestion for genotype-phenotype association. However, there are little longitudinal data evaluating the impact of specific defects on disease progression, but a recent study showed a worse lung disease and poorer nutritional status. Concluding, this report underlies the importance of patient-oriented diagnosis and management in highly experienced PCD centres.

Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort.

BACKGROUND: Primary ciliary dyskinesia (PCD), a genetically heterogeneous condition enriched in some consanguineous populations, results from recessive mutations affecting cilia biogenesis and motility. Currently, diagnosis requires multiple expert tests. METHODS: The diagnostic utility of multigene panel next-generation sequencing (NGS) was evaluated in 161 unrelated families from multiple population ancestries. RESULTS: Most (82%) families had affected individuals with biallelic or hemizygous (75%) or single (7%) pathogenic causal alleles in known PCD genes. Loss-of-function alleles dominate (73% frameshift, stop-gain, splice site), most (58%) being homozygous, even in non-consanguineous families. Although 57% (88) of the total 155 diagnostic disease variants were novel, recurrent mutations and mutated genes were detected. These differed markedly between white European (52% of families carry DNAH5 or DNAH11 mutations), Arab (42% of families carry CCDC39 or CCDC40 mutations) and South Asian (single LRRC6 or CCDC103 mutations carried in 36% of families) patients, revealing a striking genetic stratification according to population of origin in PCD. Genetics facilitated successful diagnosis of 81% of families with normal or inconclusive ultrastructure and 67% missing prior ultrastructure results. CONCLUSIONS: This study shows the added value of high-throughput targeted NGS in expediting PCD diagnosis. Therefore, there is potential significant patient benefit in wider and/or earlier implementation of genetic screening.

Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials.

Pulmonary exacerbations are a cause of significant morbidity in patients with primary ciliary dyskinesia (PCD) and are frequently used as an outcome measure in clinical research into chronic lung diseases. So far, there has been no consensus on the definition of pulmonary exacerbations in PCD. 30 multidisciplinary experts and patients developed a consensus definition for children and adults with PCD. Following a systematic review, the panel used a modified Delphi process with a combination of face-to-face meetings and e-surveys to develop a definition that can be used in research settings for children and adults with PCD. A pulmonary exacerbation was defined by the presence of three or more of the following seven items: 1) increased cough, 2) change in sputum volume and/or colour, 3) increased shortness of breath perceived by the patient or parent, 4) decision to start or change antibiotic treatment because of perceived pulmonary symptoms, 5) malaise, tiredness, fatigue or lethargy, 6) new or increased haemoptysis, and 7) temperature >38°C. The consensus panel proposed that the definition should be used for future clinical trials. The definition should be validated and the usability assessed during these studies.

Relevancia a corto plazo de la coinfección viral en pacientes menores de 2 años hospitalizados con infecciones de las vías respiratorias inferiores / Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age

Introducción: Avances en el diagnóstico molecular han hecho posible la detección de agentes virales desconocidos en infecciones de las vías respiratorias inferiores (IVRI). Sin embargo, sigue habiendo dudas relativamente a su frecuencia y relevancia. Objetivo: Comparar la clínica y la gravedad entre la infección por virus único y la coinfección en niños admitidos por IVRI. Métodos: Se realizó un estudio durante 3 años consecutivos (2012-2015) que incluyó a niños menores de 2 años ingresados por IVRI. La identificación viral se realizó mediante la técnica de PCR para 16 virus. Los datos clínicos y el uso de los recursos hospitalarios se recogieron de forma estándar durante la estancia hospitalaria y se compararon la infección única con coinfecciones virales. Resultados: Fueron analizadas 524 muestras (451 pacientes); 448 (85,5%) tuvieron al menos un virus identificado. Coinfecciones virales se encontraron en 159 (35,5%). RSV y HRV fueron los virus más frecuentes; bronquiolitis y neumonía, los diagnósticos principales. Los pacientes con coinfecciones virales eran mayores, iban a la guardería, tenían sibilancias recurrentes con más frecuencia y eran más sintomáticos al ingreso. No fueron sometidos a más exámenes, pero les fueron prescritos medicamentos con más frecuencia. El grupo de la coinfección viral no mostró una mayor duración de la estancia hospitalaria, de la necesidad de oxígeno, de UCI o soporte ventilatorio. Discusión: Nuestro estudio mostró una proporción significativa de coinfecciones virales en los niños pequeños ingresados con IVRI y confirma dados previos que muestran que la prescripción es más frecuente en las coinfecciones virales, sin asociación con peor resultado clínico (AU)

Introduction: Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. Objective: compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. Methods: A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. Results: The study included 524 samples (451 patients); 448 (85,5%) had at least one virus identified. Viral coinfections were found in 159 (35,5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. Discussion: Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome (AU)

[Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age]. / Relevancia a corto plazo de la coinfección viral en pacientes menores de 2 años hospitalizados con infecciones de las vías respiratorias inferiores.

INTRODUCTION: Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. OBJECTIVE: compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. METHODS: A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. RESULTS: The study included 524 samples (451 patients); 448 (85,5%) had at least one virus identified. Viral coinfections were found in 159 (35,5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. DISCUSSION: Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome.

Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age.

INTRODUCTION: Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. OBJECTIVE: Compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. METHODS: A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. RESULTS: The study included 524 samples (451 patients); 448 (85.5%) had at least one virus identified. Viral coinfections were found in 159 (35.5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. DISCUSSION: Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome.

INTRODUCCIÓN: Avances en el diagnóstico molecular han hecho posible la detección de agentes virales desconocidos en infecciones de las vías respiratorias inferiores (IVRI). Sin embargo, sigue habiendo dudas relativamente a su frecuencia y relevancia. OBJETIVO: Comparar la clínica y la gravedad entre la infección por virus único y la coinfección en niños admitidos por IVRI. MÉTODOS: Se realizó un estudio durante 3 años consecutivos (2012-2015) que incluyó a niños menores de 2 años ingresados por IVRI. La identificación viral se realizó mediante la técnica de PCR para 16 virus. Los datos clínicos y el uso de los recursos hospitalarios se recogieron de forma estándar durante la estancia hospitalaria y se compararon la infección única con coinfecciones virales. RESULTADOS: Fueron analizadas 524 muestras (451 pacientes); 448 (85,5%) tuvieron al menos un virus identificado. Coinfecciones virales se encontraron en 159 (35,5%). RSV y HRV fueron los virus más frecuentes; bronquiolitis y neumonía, los diagnósticos principales. Los pacientes con coinfecciones virales eran mayores, iban a la guardería, tenían sibilancias recurrentes con más frecuencia y eran más sintomáticos al ingreso. No fueron sometidos a más exámenes, pero les fueron prescritos medicamentos con más frecuencia. El grupo de la coinfección viral no mostró una mayor duración de la estancia hospitalaria, de la necesidad de oxígeno, de UCI o soporte ventilatorio. DISCUSIÓN: Nuestro estudio mostró una proporción significativa de coinfecciones virales en los niños pequeños ingresados con IVRI y confirma dados previos que muestran que la prescripción es más frecuente en las coinfecciones virales, sin asociación con peor resultado clínico.

Acute viral bronchiolitis: Physician perspectives on definition and clinically important outcomes.

BACKGROUND: Two key limitations hamper intervention research in bronchiolitis: the absence of a clear definition of disease, and the heterogeneous choice of outcome measures in current clinical trials. We assessed how paediatricians and general practitioners (GPs) perceived definition and clinically important outcomes in bronchiolitis. METHODS: A nationwide online survey (ABBA study) was conducted through the Portuguese Society of Paediatrics and GPs' mailing lists. We assessed agreement with statements on bronchiolitis definition, and participants were asked to score the relative importance of several outcomes. Principal component analysis (PCA) explored dimensions underlying disease definition. Outcomes were ranked by mean score and proportion given highest score. RESULTS: We included 514 paediatricians and 165 GPs (overall 59% were board-certified). Most paediatricians (76.5%) agreed with a definition based on coryza, wheezing and/or crackles/rales, compared to 38.1% GPs (P < 0.001). Less than 5% physicians agreed with a definition commonly used in clinical trials (<12 months, first episode of wheeze). We retained three dimensions on PCA: one based on coryza, rales/crepitations and no sudden onset; another on number of episodes and age; and a third on wheeze. Dimensions varied by physician specialization and training (P < 0.01). Hospital admission and respiratory distress were top rated outcomes by both groups of physicians. CONCLUSIONS: Physician definitions of bronchiolitis have considerable variability and often mismatch those of clinical trials. Rating of important outcomes was consistent. Our results highlight the need for a robust standardized definition of acute bronchiolitis in infants and support the development of a core outcome set for future clinical trials. Pediatr Pulmonol. 2016;51:724-732. © 2015 Wiley Periodicals, Inc.

[Growth and puberty in type 1 diabetes mellitus - experience from a pediatric endocrinology unit]. / Crescimento e puberdade na diabetes mellitus tipo 1 - experiência de uma unidade de endocrinologia pediátrica.

BACKGROUND: Type 1 Diabetes Mellitus (T1DM) is the most common endocrine-metabolic disease in children. It is associated with vascular and neuropathic complications, and may also affect growth and development. OBJECTIVE: To correlate the metabolic control and disease duration with growth and puberty in patients with T1DM followed in a Pediatric Endocrinology Outpatient Clinic. SUBJECTS AND METHODS: Retrospective analysis. Sample obtained from patients with T1DM followed in Hospital Santa Maria Pediatric Endocrinology Outpatient Clinic (Lisbon - Portugal) since 1994 until March 2011. INCLUSION CRITERIA: patients diagnosed before the onset of puberty and who had attained their final height during the follow-up. VARIABLES: sex, age, weight and height at diagnosis and final, parents' height, growth velocity, pubertal height gain, age at menarche and metabolic control during puberty. RESULTS: 39 patients, 51% female, 82% diagnosed less than five years before puberty. Fifty-four percent presented an average HbA1c between 8-10%, what we considered reasonable. There seems to be a trend towards an inverse association between HbA1c and the maximum speed of growth and pubertal height gain, although not statistically significant. These patients were taller than average at diagnosis (z-score: male 0.9; female: 0.5) and lost height during puberty, yet attained final heights within normal range and matching their target heights. CONCLUSIONS: Although HbA1c seems to negatively influence maximum growth rate and pubertal height gain, there was no compromise in final height in this group of patients.

Rastreio de patologia respiratória em crianças em idade escolar com o uso de espirometria portátil / Respiratory disease screening in school-aged children using portable spirometry

OBJETIVOS: Avaliar a prevalência de doença respiratória em crianças em idade escolar e determinar o valor da espirometria de campo. MÉTODOS: Avaliaram-se 313 alunos do primeiro e quarto ano de quatro escolas de Lisboa. Aplicou-se questionário respiratório auto-preenchido, e efetuou-se espirometria. Realizou-se análise descritiva e bivariada seguida de análise de regressão logística múltipla. RESULTADOS: Trinta e cinco por cento das crianças tiveram pelo menos um episódio de sibilância (18 por cento > 2 episódios), e 4 por cento tiveram diagnóstico de asma. Sibilância foi mais frequente com história familiar de atopia (OR ajustado = 2,7, IC95 por cento 1,4-5,1), tabagismo na gravidez, infecção respiratória baixa (IRB) (OR ajustado = 2,8; IC95 por cento 1,2-6,2), bronquiolite (OR ajustado = 3,3; IC95 por cento 1,3-8,2) e alergia a aeroalérgenos (OR ajustado = 3,2; IC95 por cento 1,4-7,2). Asma foi mais frequente com história de IRB (OR ajustado = 14,6; IC95 por cento 1,7-122,9) e alergia a aeroalérgenos (OR ajustado = 8,2; IC95 por cento 2,0-34,2). Cento e sessenta e nove (54 por cento) valores espirométricos preencheram critérios de aceitabilidade. O grupo com sibilância tinha em média valores de escore z inferiores para volume expiratório forçado no primeiro segundo (VEF1), razão entre VEF1 e capacidade vital forçada (CVF) (VEF1/CVF) e fluxo expiratório forçado entre 25 e 75 por cento (FEF25-75) (p < 0,05), além de maior percentagem de crianças com valores anormais para VEF1, VEF1/CVF e FEF25-75 (FEF25-75, p < 0,05). CONCLUSÕES: Este estudo piloto revelou frequência elevada de sintomatologia respiratória obstrutiva em escolares em Lisboa. Verificou-se boa correlação entre o questionário e os valores espirométricos. A baixa prevalência de asma leva-nos a especular que este diagnóstico esteja subestimado nesta população.

OBJECTIVES: To assess the prevalence of respiratory disease in school-aged children and to determine the value of field spirometry. METHODS: Data on 313 1st and 4th graders from four public schools in Lisbon were analyzed. A respiratory self-answered questionnaire and standard spirometry were performed. Descriptive and bivariate analysis was followed by multiple logistic regression. RESULTS: Thirty-five percent of the children presented at least one episode of wheezing (18 percent > 2 episodes), and 4 percent had asthma. Wheezing was more frequent with family history of atopy (adjusted OR = 2.7; 95 percentCI 1.4-5.1), maternal smoking during pregnancy, lower respiratory tract infection (LRTI) (adjusted OR = 2.8; 95 percentCI 1.2-6.2), bronchiolitis (adjusted OR = 3.3; 95 percentCI 1.3-8.2), and allergy to aeroallergens (adjusted OR = 3.2; 95 percentCI 1.4-7.2). Asthma was more frequent with previous history of LRTI (adjusted OR = 14.6; 95 percentCI 1.7-122.9) and allergy to aeroallergens (adjusted OR = 8.2; 95 percentCI 2.0-34.2). Fifty-five percent of spirometry measurements met the acceptability criteria of the American Thoracic Society and of the European Respiratory Society. Wheezers presented mean lower z scores for forced expiratory volume in 1 second (FEV1), ratio between FEV1 and forced vital capacity (FVC) (FEV1/FVC), and forced expiratory flow between 25 and 75 percent (FEF25-75) (p < 0.05), as well as higher percentage of abnormal FEV1, FEV1/FVC and FEF25-75 (FEF25-75, p < 0.05). CONCLUSIONS: This pilot study showed a high prevalence of obstructive airway symptoms in school-aged children in Lisbon. Symptoms assessed by the questionnaire showed good correlation with spirometric values. The small prevalence of asthma leads us to speculate that asthma is under-diagnosed in this population.

Respiratory disease screening in school-aged children using portable spirometry.

OBJECTIVES: To assess the prevalence of respiratory disease in school-aged children and to determine the value of field spirometry. METHODS: Data on 313 1st and 4th graders from four public schools in Lisbon were analyzed. A respiratory self-answered questionnaire and standard spirometry were performed. Descriptive and bivariate analysis was followed by multiple logistic regression. RESULTS: Thirty-five percent of the children presented at least one episode of wheezing (18% ≥ 2 episodes), and 4% had asthma. Wheezing was more frequent with family history of atopy (adjusted OR = 2.7; 95%CI 1.4-5.1), maternal smoking during pregnancy, lower respiratory tract infection (LRTI) (adjusted OR = 2.8; 95%CI 1.2-6.2), bronchiolitis (adjusted OR = 3.3; 95%CI 1.3-8.2), and allergy to aeroallergens (adjusted OR = 3.2; 95%CI 1.4-7.2). Asthma was more frequent with previous history of LRTI (adjusted OR = 14.6; 95%CI 1.7-122.9) and allergy to aeroallergens (adjusted OR = 8.2; 95%CI 2.0-34.2). Fifty-five percent of spirometry measurements met the acceptability criteria of the American Thoracic Society and of the European Respiratory Society. Wheezers presented mean lower z scores for forced expiratory volume in 1 second (FEV1), ratio between FEV1 and forced vital capacity (FVC) (FEV1/FVC), and forced expiratory flow between 25 and 75% (FEF25-75) (p < 0.05), as well as higher percentage of abnormal FEV1, FEV1/FVC and FEF25-75/ (FEF25-75, p < 0.05). CONCLUSIONS: This pilot study showed a high prevalence of obstructive airway symptoms in school-aged children in Lisbon. Symptoms assessed by the questionnaire showed good correlation with spirometric values. The small prevalence of asthma leads us to speculate that asthma is under-diagnosed in this population.

[Bacille Calmette-Guérin adenitis: diagnostic and therapeutic guidelines]. / Adenite do bacilo Calmette-Guérin: protocolo diagnóstico e terapêutico.

Bacille Calmette-Guérin (BCG) vaccination is occasionally associated with lymphadenitis, called BCGitis, and only rarely can it occur in the setting of immunodeficiency. We report six cases of BCGitis admitted to our hospital (2005-7) for surgical treatment: five were male, in all cases BCG was given at birth; median age at presentation was 5.5 months. Three children had spontaneous drainage, and one child had two lymph node regions involved (axillary and supraclavicular). Five required surgical drainage due to suppuration or persistence of lymphadenopathy. The patient with multiple lymph node involvement was treated with antimycobacterial therapy for suspected primary immunodeficiency, which was never confirmed. Immune function studies were normal in all cases. Average follow-up was 15 months. The therapeutical approach of suppurative lymphadenitis and the decision to investigate an underlying immunodeficiency is not consensual. We think that in the absence of disseminated disease an expectant attitude should be adopted.

[Multi-drug-resistant tuberculosis in a Department of Infectious Diseases]. / Tuberculose multirresistente.

In Western Europe, Portugal has the highest incidence of tuberculosis (TB) as well as HIV infection. At the Department of Infectious Diseases, Hospital de Santa Maria, Lisbon, we have observed a steady increase in cases of drug resistant (DR) and multi-drug resistant (MDR) TB over the last few years. To identify the determinants of drug- resistant tuberculosis, clinical notes from all patients admitted to the Department of Infectious Diseases from 1995 to 2000, with DR- or MDR-TB were retrospectively reviewed. A total of 212 samples, from 190 patients with tuberculosis were tested for sensitivity to first line anti-TB drugs, using standard methods. Most patients (61%) were intravenous drugs users. Resistance to at least one drug was found in 44 patients (23%); notes were available for review in 39 (36 HIV infected) patients. The rate of DR-TB was 9% (n=16) and that of MDR-TB was 15% (n=28). Almost half of the MDR-TB cases (n=13) showed resistance to four drugs (HRSE). Thirteen patients (69%) were first diagnosed as fully sensitive tuberculosis, during their first admission to the Department; however, later on they developed MDR-TB or DR-TB. Non-compliance with therapy and the intravenous use of drugs were associated with MDR-TB. The large increase in MDR-TB in our Department is of great concern. The clustering of identical resistance patterns suggest transmission of TB from a single source patient that may well have occurred in a nosocomial context. Traditional tuberculosis control measures seem to be insufficient in settings were prevalence of HIV infection and tuberculosis are high. This becomes even more important when the incidence of intravenous substance abuse, and often non-compliance, are predominant factors. Appropriate isolation facilities for all suspected tuberculosis cases as well as rapid diagnostic and drug susceptibility tests will be required to prevent further spread of MDR-TB.