Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions.From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age.The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels.This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.

It was the purpose of the present investigation to monitor the composition of the subgingival microbiota at selected sites in individuals passing through puberty and to correlate observed changes with the development of pubertal maturation. Between the ages of 11 and 14 years, pubertal and skeletal maturation was monitored annually in 22 boys and 20 girls. During this time, subgingival microbial samples were taken every 4th to 5th month (10 times in 4 years) mesially of the upper first molars. High values in total bacterial counts were reached after the onset of puberty, followed by a decrease towards the end of the observation period. The frequency of detection of Actinomyces odontolyticus and of Capnocytophaga sp. increased with time. The frequencies of other selected species, specifically of black pigmenting Bacteriodes sp. were not found to increase when tested by linear and quadratic models of time trend. However, a statistically significant rise in the frequency of detecting B. intermedius and B. melaninogenicus was noted in the initial pubertal phase identified by the onset of testicular growth in boys (p = 0.05). A significant relationship also existed between testes growth and increase of A. odontolyticus (p less than 0.01). In girls, a similar increase was obtained for A. odontolyticus when studied in relation to the Tanner scores for breast development (p less than 0.01). The changes observed in the subgingival microbiota during puberty may be related to the development of gingivitis, which was demonstrated by a higher tendency for gingival bleeding during the course of the pubertal maturation process.

In association studies, micro-organisms can only be recognized as suspects for playing a major rôle in the development of a pathological environment, if their destructive action goes along with a marked proportional increase of their numbers or if their first detection can be related to the clinical onset of the disease. Limitations in the reproducibility of repeated samples have to be taken into account, when changes of the microbial composition of subgingival environments are to be studied, and when local clinical changes are to be related to shifts in the composition of the pertaining microbiological compartment. To study reproducibility, a total of 109 sites was sampled repeatedly with sterile paperpoints at an interval of 7 to 10 days in 24 patients suffering from periodontal disease and 12 edentulous patients wearing successful and failing osseointegrated titanium implants. Using continuous anaerobic techniques, the samples were cultured on nonselective and selective media and were studied by darkfield microscopy. Both the intertest-agreements of frequencies of detection (kappa-statistics) as well as the discrepancies of proportions of bacterial groups and selected bacterial species were determined. The standard deviation of proportional differences between first and second samples ranged between 6.4% (fusiform organisms) and 17.2% (coccoid cells) for darkfield parameters, between 4.3% (B. melaninogenicus on ETSA/Kana.) and 14.0% (B. gingivalis on ETSA/Kana.) for selected bacterial species and between 6.9% (gram-negative anaerobic cocci) and 24.0% (gram-positive facultative cocci) for bacterial groups classified according to gram stain characteristics and atmospheric growth conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

In this paper we give an informal introduction to a robust method for survival analysis which is based on a modification of the usual partial likelihood estimator (PLE). Large sample results lead us to expect reduced bias for this robust estimator compared with the PLE whenever there are even slight violations of the model. In this paper we investigate three types of violation: (a) varying dependency structure of survival time and covariates over the sample; (b) omission of influential covariates, and (c) errors in the covariates. The simulations presented support the above expectation. Analyses of data sets from cancer epidemiology and from a clinical trial in lung cancer illustrate that a better fit and additional insights may be gained using robust estimators.

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