Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies

The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing

Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

Computerized respiratory sounds can differentiate smokers and non-smokers

Cigarette smoking is often associated with the development of several respiratory diseases however, if diagnosed early, the changes in the lung tissue caused by smoking may be reversible. Computerised respiratory sounds have shown to be sensitive to detect changes within the lung tissue before any other measure, however it is unknown if it is able to detect changes in the lungs of healthy smokers. This study investigated the differences between computerised respiratory sounds of healthy smokers and non-smokers. Healthy smokers and non-smokers were recruited from a university campus. Respiratory sounds were recorded simultaneously at 6 chest locations (right and left anterior, lateral and posterior) using air-coupled electret microphones. Airflow (1.0–1.5 l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals and respiratory sounds with validated algorithms. Forty-four participants were enrolled: 18 smokers (mean age 26.2, SD = 7 years; mean FEV1 % predicted 104.7, SD = 9) and 26 non-smokers (mean age 25.9, SD = 3.7 years; mean FEV1 % predicted 96.8, SD = 20.2). Smokers presented significantly higher frequency at maximum sound intensity during inspiration [(M = 117, SD = 16.2 Hz vs. M = 106.4, SD = 21.6 Hz; t(43) = −2.62, p = 0.0081, d z = 0.55)], lower expiratory sound intensities (maximum intensity: [(M = 48.2, SD = 3.8 dB vs. M = 50.9, SD = 3.2 dB; t(43) = 2.68, p = 0.001, d z = −0.78)]; mean intensity: [(M = 31.2, SD = 3.6 dB vs. M = 33.7,SD = 3 dB; t(43) = 2.42, p = 0.001, d z = 0.75)] and higher number of inspiratory crackles (median [interquartile range] 2.2 [1.7–3.7] vs. 1.5 [1.2–2.2], p = 0.081, U = 110, r = −0.41) than non-smokers. Significant differences between computerised respiratory sounds of smokers and non-smokers have been found. Changes in respiratory sounds are often the earliest sign of disease. Thus, computerised respiratory sounds might be a promising measure to early detect smoking related respiratory diseases

EAACI position paper on occupational rhinitis

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item

Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer

Terminologia da ausculta pulmonar utilizada em publicações médicas brasileiras, no período de janeiro de 1980 a dezembro de 2003 Pulmonary auscultation terminology employed in Brazilian medical journals between January of 1980 and December of 2003

OBJETIVO: Avaliar a adequação de uso de termos semiológicos da ausculta pulmonar em publicações médicas brasileiras sobre doenças respiratórias, no período de janeiro de 1980 a dezembro de 2003. MÉTODOS: Realizou-se um estudo descritivo, analisando-se três revistas médicas: Jornal de Pneumologia, Jornal de Pediatria e Revista Médica Brasileira. Foram selecionados os artigos originais e relatos de casos sobre doenças respiratórias, de onde foram extraídos os termos semiológicos da ausculta pulmonar. Foi avaliada a adequação dos termos na descrição dos ruídos adventícios. RESULTADOS: Encontrou-se maior inadequação no uso dos termos de ruídos descontínuos, comparado com o uso dos termos de ruídos contínuos (87,7% versus 44%, p = 0,0000). Não houve diferença significativa entre relatos de pneumologistas e de outros especialistas quanto à inadequação no uso dos termos (56,5% versus 62,0%, p = 0,26). Também não observamos diferença significativa entre as regiões do país e os períodos antes e após a divulgação da nomenclatura internacional. CONCLUSÃO: O uso inadequado dos termos para descrever ruídos adventícios na ausculta pulmonar continua sendo um fenômeno freqüente e geral nas publicações médicas brasileiras.<br>OBJECTIVE: To evaluate the appropriateness of the use of auscultation terminology in Brazilian respiratory disease-related medical journals published between January of 1980 and December of 2003. METHODS: A descriptive study was conducted, evaluating three medical journals: the Jornal de Pneumologia (Journal of Pulmonology), Jornal de Pediatria (Journal of Pediatrics) and Revista Brasileira de Medicina (Brazilian Journal of Medicine). Original articles and case reports about respiratory diseases were selected, and auscultation terminology was extracted from these articles. The appropriateness of terms used to describe adventitious sounds was assessed. RESULTS: We found that the inappropriate use of terms was more frequent when intermittent sounds were described than when continuous sounds were described (87.7% versus 44.0%; p = 0.0000). No significant difference was observed between the inappropriate use of terms by pulmonologists and that observed for other specialists (56.5% versus 62.0%; p = 0.26). In addition, there were no significant differences among the various regions of the country or between the periods prior to and after the dissemination of international nomenclature. CONCLUSION: Inappropriate use of pulmonary auscultation terms describing adventitious sounds remains common and widespread in Brazilian medical publications