In patients with cystic fibrosis and mild lung disease, high-dose ibuprofen, taken consistently for four years, significantly slows the progression of the lung disease without serious adverse effects.

No abstract

Rapid progress in cystic fibrosis research affords the possibility of halting the progress of the lung disease. We used data from 215 patients who had sputum cultures negative for Burkholderia cepacia, at least one outpatient pulmonary function test during 1990, and at least one test a year later to estimate the number of subjects and study duration required to demonstrate that a hypothetical treatment reduces the rate of decline of forced expiratory volume in 1 s (FEV1) to zero. Mean rate of decline of FEV1 (percent predicted) was about 2% predicted per year. Variability decreases with increasing time of observation. For a 1-y study, with alpha = 0.05 and beta = 0.20, over 550 patients must complete the study in each group to show that a treatment halts pulmonary decline. For a 2-y study, 86 subjects in each group are required, and for 4 y, 65. Increasing the number of data points used to determine the rate of decline of FEV1 had only small effect on sample size. Use of pulmonary function data collected at regular intervals for research purposes did not alter these conclusions. Higher initial FEV1 was associated with a greater rate of decline, and among patients with initial FEV1 > 60% predicted, younger subjects had a faster decline than did older subjects. Thus, fewer subjects will be required to detect a complete halt in progression of lung disease if the patients are young and have mild pulmonary disease.

The adolescent spurt in 230 children with cystic fibrosis (CF) treated at the Cleveland CF centre in northeastern Ohio was compared to that found in normal children from the Fels Longitudinal Growth Study in southwestern Ohio. The Preece-Baines Model 1 (PB1) growth equation was applied to longitudinal height data from both samples to describe a large number of data points for each child in terms of a few biologically meaningful parameters, such as age, height, and velocity at the take-off and peak of the adolescent growth spurt. The growth spurt is delayed by an average of 0.8 years and is about 1 cm/year slower at its peak in CF patients compared to the normal controls. This delay should be considered when comparing clinical growth measurements of adolescent CF patients with normal standards. Peak velocity is lower than expected, even for late-maturing normal children, and height at take-off, peak velocity, and adulthood is significantly reduced, especially in boys. These findings are consistent with the clinical impression that the growth spurt is delayed and attenuated in CF patients, particularly those with poor pulmonary function. Girls homozygous for the delta F508 mutation have significantly more growth retardation than those with other CF mutations.

To evaluate the extent and nature of the variability of measurements of upper airway area by acoustic reflection (AAAR), we made repeated measures of pharyngeal AAAR in 10 normal adult volunteers. We selected mean pharyngeal area as a better index of upper airway size than peak pharyngeal area or pharyngeal volume. Within-run variability of this measure was 8 +/- 4% (SD) (coeff of variation). This variability could not be explained by changes in lung volume or differences in phase of respiration. Five subjects had tracheal and pharyngeal area measured by using both the custom-made wax mouthpiece (W) and a commercial rubber pulmonary function mouthpiece (R). Reproducibility of pharyngeal AAAR was within 10% (coeff of variation) using R, but measurements of pharyngeal AAAR varied with the different types of mouthpiece, as W/R ranged from 0.72 to 1.70. In contrast, measurements of midtracheal area were similar for both mouthpiece types [mean W/R = 0.97 +/- 14 (SD)]. The acoustic reflection technique yields a reproducible index of pharyngeal size that does not vary with phase of respiration or modest changes in lung volume. Either W or R may be used to make clinical measurements, but the type of mouthpiece should be consistent and specified.

To determine whether airway size correlates with measures of lung or body size, we used the acoustic reflection technique to calculate tracheal cross-sectional area in 103 healthy young adults. Men have significantly larger tracheas than women [2.48 +/- 0.08 vs. 1.91 +/- 0.05 (SE) cm2, P less than 0.001]. Within each sex, there is no correlation between tracheal size and body size or maximal expiratory flows. There is a significant positive correlation between tracheal area and vital capacity in males only (r = 0.36, P less than 0.01). These results support the concept of dysanapsis, relatively independent growth of the airways and lung parenchyma, as well as sex-related differences in airway size and growth. Inherent airway size may be a factor in the development and/or progression of lung disease.

Skin color has long been of interest to human geneticists and often used as an example of a human quantitative trait under relatively wellunderstood genetic control. Although the basic biology of melanin production and the method of measurement are areas in which skin color studies are fairly well advanced, compared to other quantitative traits, the evolutionary significance and mode of inheritance are still being debated. In view of the many steps involved in the production and dispersion of melanin and the large number of loci involved in coat color of laboratory animals, it is suggested that genetic control of human skin color must be fairly complex. Studies that have found evidence for relatively few loci effecting the differences between racial groups may either be using inappropriate methods, or they may be concentrating attention on only that portion of genetic variability that distinguishes between major world groups, particularly blacks and whites. Genetic analysis of intermediate groups and pedigree analysis of rare pigmentation conditions may yield more information on skin color genetics.Human skin color is a classic case of quantitative variation. A strong genetic component is generally assumed, based on the obvious differences among world populations, yet the effect of environmental sunlight in the form of tanning cannot be disputed. It is also important that skin color can be assessed on a continuous measurement scale. The goal of quantitative genetics is to determine the relative contributions of the genetic and environmental components to the phenotype and to elucidate the mode of inheritance for the genetic component, and several steps have been taken in this direction in the study of skin color genetics.The techniques of quantitative genetics were developed in the context of controlled genetic crosses in laboratory animals or plants. Because this approach cannot be taken with human subjects, human geneticists have learned to take advantage of naturally occurring situations that approximate the genetic experiments designed by biologists, Skin color is the most suitable of human quantitative traits in this respect because variation among groups is much larger than within groups, so that admixture of groups from the two extremes approximates a cross between inbred strains of laboratory animals. While there are faults with this analogy, the high visibility of skin color variability makes hybrid individuals easy to identify, and historical events have resulted in several hybrid populations appropriate for study. In addition, portable, objective measurement techniques have been introduced in recent years, and a good understanding of the basic biology of pigmentation has developed after several decades of study.

Data on 40 anthropometric measurements from 144 nuclear families in Chandigarh, India, are presented. Most families contain a pair of monozygotic or dizygotic twins, one or more singleton siblings, and their parents. Familial correlations for age-sex standardized, normalized measurements are estimated by maximum likelihood for marital, parent-child, sibling, and twin pairs. Heterogeneity tests for sex-specific subtype correlations male-male, male-female, female-female) indicate that the sex of the relative plays no significant role in the magnitude of the familial correlations except for maternal effects and differences among male and female twin pairs for a few of the variables. Marital correlations are high for body measurements, but not for head or face variables. Twin correlations seem to indicate a higher level of heritability than correlations from other family members.