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BACKGROUND: Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC). METHODS: Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated. RESULTS: Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81â years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age. CONCLUSIONS: Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.
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BACKGROUND: In the last decade, a fundamental shift in the treatment of cystic fibrosis (CF) took place due to the introduction of CF transmembrane conductance regulator (CFTR) modulators. Adequate medication adherence is a prerequisite for their effectiveness, but little is known about adherence to CFTR modulators. We aimed to assess the extent of medication adherence to CFTR modulators in patients with CF and assess which characteristics are associated with adherence. METHODS: A systematic review following PRISMA guidelines was performed. Studies needed to report adherence to CFTR modulators. Main outcomes were: 1) level of medication adherence and 2) associations of demographic and/or clinical characteristics with adherence. RESULTS: In total, 4082 articles were screened and 21 full-text papers were assessed for eligibility. Ultimately, seven studies were included. Most studies were retrospective and focused on adherence to ivacaftor or lumacaftor-ivacaftor with only one focusing on elexacaftor-tezacaftor-ivacaftor. The majority used pharmacy refill data with adherence determined with the proportion of days covered (PDC) or the medication possession ratio (MPR). One study additionally used electronic monitoring and patient self-reported adherence. Adherence was 0.62-0.99 based on pharmacy data (PDC or MPR), 61% via electronic monitoring and 100% via self-report. Age <18â years appeared to be associated with good adherence, as was a higher lung function. CONCLUSIONS: Despite the wide variety of adherence methods used, adherence to CFTR modulators is suboptimal, based on objective measures such as pharmacy refill data or electronic monitoring. CFTR modulator adherence measurement and definitions requires more standardisation with a preference for objective and granular methods.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Adesão à Medicação , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Resultado do Tratamento , Agonistas dos Canais de Cloreto/uso terapêutico , Quinolonas/uso terapêutico , Feminino , Masculino , Adolescente , Adulto Jovem , Combinação de Medicamentos , Adulto , Criança , Aminofenóis/uso terapêutico , Aminopiridinas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pré-Escolar , BenzodioxóisRESUMO
BACKGROUND: The introduction of modulator therapy for cystic fibrosis (CF) has led to an increased interest in the detection of small airway disease (SAD) as sensitive marker of treatment response. The particles in exhaled air (PExA) method, which records exhaled particle mass (PEx ng/L) and number (PExNR), detects SAD in adult patients. Our primary aim was to investigate if PExA outcomes in children with CF are different when compared to controls and associated with more severe disease. Secondary aims were to assess feasibility and repeatability of PExA in children with CF and to correlate PExA to multiple breath nitrogen washout (MBNW) as an established marker of SAD. METHODS: Thirteen healthy children (HC), 17 children with CF with normal lung function (CF-N) (FEV1 z-score ≥ -1.64) and six with airway obstruction (CF-AO) (FEV1 z-score < -1.64) between 8 and 18 years performed MBNW followed by PExA and spirometry. Children with CF repeated the measurements after 3 months. RESULTS: PEx ng/L and PExNR/L per liter of exhaled breath were similar between the three groups. The lung clearance index (LCI) was significantly higher in both CF-N and CF-AO compared to HC. All participants, except one, were able to perform PExA. Coefficient of variation for PEx ng/l was (median) 0.38, range 0-1.25 and PExNR/l 0.38, 0-1.09. Correlation between LCI and PEx ng/l was low, rs 0.32 (p = .07). CONCLUSION: PExA is feasible in children. In contrast to LCI, PExA did not differentiate healthy children from children with CF suggesting it to be a less sensitive tool to detect SAD.
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Asma , Fibrose Cística , Criança , Adulto , Humanos , Testes de Função Respiratória/métodos , Espirometria/métodos , Expiração , Nitrogênio , Testes Respiratórios/métodos , PulmãoRESUMO
BACKGROUND: It is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper-responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood. METHODS: We searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21-26) and include at least one candidate risk factor. RESULTS: Of the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow-up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non-affected individuals until peak function was attained. CLINICAL IMPLICATIONS AND FUTURE RESEARCH: Deficits in lung function growth develop in early childhood, and children with asthma, BHR and early-life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at-risk subjects and provide treatment aimed at preventing long-term sequelae of lung function.
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Asma , Hiper-Reatividade Brônquica , Hipersensibilidade , Adulto , Asma/epidemiologia , Hiper-Reatividade Brônquica/epidemiologia , Criança , Pré-Escolar , Humanos , Hipersensibilidade/epidemiologia , Pulmão , Sons Respiratórios , Adulto JovemRESUMO
Multiple-breath nitrogen washout (MBNW) and its clinical parameter lung clearance index (LCI) are gaining increasing attention for the assessment of small airway function. Measurement of LCI relies on accurate assessment of functional residual capacity (FRC). The EasyOne Pro LAB (ndd) and Exhalyzer D (EM) are two commercially available MBNW devices. The aim of the study was to compare these two devices in vitro and in vivo in healthy subjects with regard to FRC, LCI and secondary outcome parameters and to relate FRCMBNW to FRC measured by body plethysmography (pleth) and helium dilution technique. MBNW measurements were performed using a lung model (FRC between 500 and 4000â mL) in vitro and in 38 subjects aged 6-65 years followed by helium dilution and pleth in vivo using fixed and relaxed breathing techniques. In vitro accuracy within 5% of lung model FRC was 67.3% for ndd, FRC was >5% higher for EM in all tests. In vivo, FRCpleth ranged from 1.2 to 5.6â L. Mean differences (limits of agreement) between FRCpleth and FRCMBNW were -7.0%, (-23.2 to 9.2%) and 5.7% (-11.2 to 22.6%) using ndd and EM, respectively. FRCndd was consistently lower than FRCEM (-11.8% (-25.6 to 2%)). LCI was comparable between the two devices (-1.3% (-21.9 to 19.3%)). There was a difference of >10 % in LCI in 12 of 38 subjects. Using the most recent software updates, both devices show relevant deviations in FRC measurement both in vitro and in vivo and individual differences in LCI in a significant proportion of subjects. The devices are therefore not interchangeable.
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Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/fisiopatologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Hemodinâmica , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Adolescente , Obstrução das Vias Respiratórias/etiologia , Feminino , Humanos , Doenças Raras/diagnóstico por imagem , Disfunção Ventricular Direita/diagnósticoRESUMO
INTRODUCTION: Prolonged neutropenia in patients with acute myeloid leukemia (AML), relapsed acute lymphoblastic leukemia (r-ALL), myelodysplastic syndrome (MDS), and those receiving hematopoietic stem cell transplantation (HSCT), is a well-known risk factor for infectious complications. Few data are available about the incidence and etiology of infectious episodes during the total treatment period associated with a decreased immunity. METHODS: Between January 2000 and December 2005 children diagnosed with AML, r-ALL, and MDS, and post-HSCT patients were included in the study. A retrospective review based on microbiological data was performed to describe the incidence and etiology of the infectious complications during the total treatment period. RESULTS: One hundred and thirty disease-specific patient episodes were included. Forty-two percent of 184 microbiologically proven infectious episodes were diagnosed in patients receiving chemotherapy, and 58% occurred in HSCT patients. During neutropenia, 123 (67%) infectious episodes were diagnosed; of the isolated species 83% were bacterial, 6% fungal, and 11% viral. In the period without neutropenia, 61 (33%) infectious episodes were diagnosed, with 38% bacterial, 3% fungal, and 59% viral species isolated. Of the infectious episodes diagnosed in patients treated with an HSCT, 52% (n = 55) occurred in the post-engraftment period. In contrast, in patients treated with chemotherapy, 92% of the infectious episodes were diagnosed during neutropenia. CONCLUSION: The number of proven infectious episodes in post-HSCT patients was not influenced by the presence of neutropenia, while in patients receiving chemotherapy significantly lower numbers of proven infectious episodes were diagnosed outside the neutropenic period.
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Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/complicações , Neutropenia/complicações , Adolescente , Infecções Bacterianas/complicações , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Lactente , Infecções/epidemiologia , Infecções/etiologia , Leucemia , Masculino , Micoses/complicações , Micoses/epidemiologia , Micoses/microbiologia , Neutropenia/epidemiologia , Neutropenia/etiologia , Viroses/complicações , Viroses/epidemiologia , Viroses/virologiaRESUMO
A term-born boy presented with a rash immediately post partum, consisting of erosions, crusts and a few vesicles. Skin biopsy showed dermal infiltration of S100 and CD1a immunopositive histiocytes. The diagnosis was 'congenital Langerhans cell histiocytosis of the skin'.
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Histiocitose de Células de Langerhans/congênito , Histiocitose de Células de Langerhans/diagnóstico , Dermatopatias/diagnóstico , Pele/patologia , Antígenos CD1/análise , Biópsia , Humanos , Recém-Nascido , Masculino , Período Pós-Parto , Proteínas S100/análiseRESUMO
A 2-year-old boy presented with a 1.5-year history of recurrent cough, wheeze and feeding problems. An x-ray of the thorax and an oesophagogram showed constriction of the trachea and proximal portion of the oesophagus. On endoscopy a foreign body was found, embedded in extensive granulation tissue. This could only be removed surgically via oesophagotomy, and turned out to be a plastic toy coin.
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Esôfago , Corpos Estranhos/diagnóstico , Corpos Estranhos/cirurgia , Pré-Escolar , Humanos , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
Disseminated aspergillosis in immunocompromised patients has a mortality rate of almost 100%. Despite the development of new antifungal agents, the outcome of disseminated aspergillosis has only improved slightly, particular in patients with central nervous system (CNS) involvement. The use of combination antifungal therapy might improve the dismal outcome of disseminated aspergillosis. We describe a critically ill adolescent with acute lymphoblastic leukemia who was successfully treated with voriconazole and caspofungin for disseminated aspergillosis with involvement of the lung, brain and thyroid gland.