Advances in cystic fibrosis: bringing the bench to the bedside.
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Cystic Fibrosis↗
Biomedical subjects
L M Taussig
Publications and source records attributed to L M Taussig.
Association of interleukin-2 and interferon-gamma production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy.
The mechanisms regulating the onset of atopic sensitization in human beings are not yet fully clarified. We assessed the capacity of mitogen-stimulated umbilical and peripheral blood mononuclear cells to produce interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) at birth and at 9 months of age in 159 infants. Mononuclear cell production of both IFN-gamma and IL-2 at 9 months, but not at birth, was found to be inversely related to parental immediate skin test reactivity to seven local aeroallergens. Skin test reactivity at the age of 6 years was also inversely related to IFN-gamma and IL-2 production at 9 months of age. However, no relationship was evident between total serum IgE levels at 6 years and production of these cytokines at 9 months. The proportions of circulating lymphocytes and CD4+ or CD8+ cells were also unrelated to skin test reactivity at the age of 6 years. These data suggest that mechanisms regulating skin test reactivity to inhaled allergens may involve deficient IFN-gamma production, deficient IL-2 production, or both during or preceding the time of initial sensitization and that additional mechanisms are involved in regulating total serum IgE level.
Adult↗
Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels. Group Health Medical Associates.
BACKGROUND: The role of lower respiratory tract illnesses (LRIs) in the development of allergies is not well understood. The relation of wheezing and non-wheezing LRIs to serum IgE levels and atopy was studied in 888 children. METHODS: Total serum IgE levels were measured at birth, nine months and six years of age; and interferon gamma production by blood mononuclear cells was measured at birth and nine months. Atopy was determined by skin prick tests at age six. Wheezing and non-wheezing LRIs up to age three were diagnosed by a physician. RESULTS: Cord serum IgE levels were similar between all LRI groups and the no LRI group. Children who had wheezing LRIs until the age of three had IgE levels at nine months and at six years within normal ranges for age. In contrast, children who had a non-wheezing LRI before the nine month IgE sample had lower IgE levels at nine months and six years (geometric mean 1.8 IU/ml and 9.9 IU/ml, respectively) compared with children who had no LRIs (3.9 IU/ml and 38.3 IU/ml, respectively). Children who had non-wheezing LRIs after the nine month IgE sample had normal nine month IgE levels (3.2 IU/ml) but decreased IgE levels at six years of age (15.7 IU/ml). Children with more than one non-wheezing LRI before the age of three were less likely to be atopic than those with no LRI (odds radio 0.2). Interferon gamma production was higher in the non-wheezing LRI group at nine months than in the no LRI or wheezing LRI groups. CONCLUSIONS: Non-wheezing LRIs are associated with subsequent depression of IgE levels and reduced skin test reactivity.
Child, Preschool↗
Passive smoke exposure and otitis media in the first year of life. Group Health Medical Associates.
OBJECTIVE: This study examined, in a health maintenance organization population of children, the associations between parents' smoking and otitis media (OM) in their children while controlling for other known risk factors. METHODS: Healthy newborns (1246) in a large health maintenance organization were enrolled at birth, and 1013 (81%) were followed prospectively for the first year of life. Their medical records were reviewed for the diagnosis of otitis media. Information on risk factors for recurrent OM (ROM) was collected, including a number of variables related to parental smoking. RESULTS: After controlling for other known risk factors for ROM including gender, day care, other siblings in the home, parental history of hay fever, and method of feeding, it was found that heavy maternal smoking of 20 or more cigarettes per day was a significant risk factor for ROM but not for nonrecurrent otitis. Heavy maternal smoking was associated with a threefold risk for ROM if the infant weighed less than the mean at birth (3.5 kg) after controlling for other risk factors. No association was found with paternal smoking. CONCLUSIONS: Heavy maternal smoking is a significant risk factor for ROM in the first year of life. This smoking effect seems to be stronger among infants of lower birth weight.
Analysis of Variance↗
The effect of paternal smoking on the birthweight of newborns whose mothers did not smoke. Group Health Medical Associates.
We examined the relationship of paternal smoking habits to birthweight in a cohort of infants enrolled at birth (n = 1219). To assess validity of parental smoking reports, cord serum levels of cotinine were measured in 175 newborns. A mean birthweight deficit of 88 g was found in newborns of nonsmoking mothers whose fathers smoked more than 20 cigarettes/day. Only 2 of 138 newborns whose mothers said they were nonsmokers had cotinine levels indicating that their mothers were active smokers. Among infants of nonsmoking mothers, detectability of cotinine in cord blood was significantly correlated with the number of cigarettes smoked daily by fathers. These data suggest that fetal growth may be adversely affected when the mother is passively exposed to tobacco smoke during pregnancy.
Adult↗
Epidemiology of physician-diagnosed allergic rhinitis in childhood.
OBJECTIVE: To investigate the natural history of and risk factors for allergic rhinitis in the first 6 years of life. METHODS: Parents of 747 healthy children followed from birth completed a questionnaire when the child was 6 years old. Data were obtained regarding physician-diagnosed allergic rhinitis (PDAR), associated symptoms, and age at onset. Risk-factor data were taken from earlier questionnaires, and data regarding immunoglobulin E (IgE) and skin-test reactivity were obtained at age 6. RESULTS: By the age of 6, 42% of children had PDAR. Children whose rhinitis began in the first year of life had more respiratory symptoms at age 6 and were more likely to have a diagnosis of asthma. Early introduction of foods or formula, heavy maternal cigarette smoking in the first year of life, and higher IgE, as well as parental allergic disorders, were associated with early development of rhinitis. Risk factors for PDAR that remained significant in a multivariate model included maternal history of physician-diagnosed allergy (odds ratio: 2.2, 95% confidence interval: 1.35-3.54), asthma in the child (4.06, 2.06-7.99), and IgE greater than 100 IU/mL at age 6 (1.93, 1.18-3.17). The odds for atopic as opposed to nonatopic PDAR were significantly higher only among those with high IgE and those who had dogs. CONCLUSION: Allergic rhinitis developing in the first years of life is an early manifestation of an atopic predisposition, which may be triggered by early environmental mental exposures.
Age of Onset↗
Evidence for Mendelian inheritance of serum IgE levels in Hispanic and non-Hispanic white families.
Considerable evidence is available suggesting a significant genetic component in the pathogenesis of asthma, but the mechanism of inheritance is not well understood. The main objective of this study was to assess if total serum IgE level, a known intermediate phenotype for asthma, is under the control of a major autosomal gene. We studied nuclear families participating in the Tucson Children's Respiratory Study in Tucson and originally selected because they belonged to a health maintenance organization. One hundred twenty-five Hispanic and 673 non-Hispanic White nuclear families were eligible; 50 Hispanic families (with 191 subjects) and 241 non-Hispanic White families (with 886 subjects) were included. Prevalence of asthma, hay fever, and parental smoking was similar among eligible families who were included and those who were not. Segregation analyses using regressive models for continuous traits showed that the best fit to the data was given by a model of Mendelian codominant inheritance of a major autosomal gene associated with higher serum IgE level. Log-likelihood for this model was not significantly different from that of the best-fitting ("unrestricted") model (P = .3) and was significantly better than log-likelihood for a dominant model (P < .0001) and a recessive model (P < .0001). An environmental model showed significant departure (P < .0001) from the unrestricted model. Tests for genetic heterogeneity showed no significant difference between the two ethnic groups. The data strongly suggest that total serum IgE levels are controlled by a major autosomal codominant gene.
Arizona↗
Cystic Fibrosis Foundation consensus conference report on pulmonary complications of cystic fibrosis.
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Child↗
Gender related differences in airway tone in children.
The effects of gender, volume history, and inhaled atropine and isoproterenol on lung mechanics were assessed in 16 normal boys and 14 normal girls using lung volumes, flow-volume curves, and oscillatory resistances. Flows were measured from full and partial forced expiratory flow-volume curves. Six girls and 6 boys were studied before and after inhaled atropine, and 10 boys and 8 girls before and after inhaled isoproterenol. Girls demonstrated a significant increase in flows on full and partial curves with a deep inspiration [Vmax-partial 0.73 +/- 0.34 (SD) to Vmax-full 0.80 +/- 0.37 and 0.83 +/- 0.20 to 1.06 +/- 0.29 TLC/s in each group] and following inhalation of isoproterenol on the partial curves only (0.73 +/- 0.34 to 0.93 +/- 0.40 TLC/s). Boys showed a small but significant increase in Vmax with isoproterenol on full curves but not on partial curves. Following atropine, boys demonstrated a significant increase in Vmax on partial flow-volume curves (0.78 +/- 0.28 to 1.00 +/- 0.35 TLC/s) and a significant decrease in specific respiratory resistance (7.6 +/- 2.7 to 5.1 +/- 0.9 cmH2O/s), whereas girls had no such changes. These data suggest that boys have greater resting airway tone than girls and that this tone is less responsive to deep inspiration and isoproterenol independently, although a combination of isoproterenol and a deep inspiration will produce increased flows in boys. Atropine reduces airway tone predominantly in boys, suggesting that the increased resting airway tone in boys is partially mediated via the vagus nerve.
Airway Resistance↗
Parental childhood respiratory illness and respiratory illness in their infants. Group Health Medical Associates.
Parental histories of childhood respiratory trouble (CRT) were examined as risk factors for lower respiratory tract illnesses in healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona. A parental history of childhood respiratory trouble before age 16 was a risk factor for infantile lower respiratory tract illnesses (LRIs). Early age of onset of the parental CRT and those illnesses described as asthma or bronchiolitis showed the greatest risk: odds ratio = 2.8, P < 0.05. After controlling for known and suspected confounders, a parental history of CRT described as asthma or bronchiolitis with onset before age 3 was associated with wheezing LRIs in their children, with an odds ratio of 2.6, P < 0.05. A parental history of CRT described as bronchitis/croup was associated with nonwheezing LRIs in their children: odds ratio = 2.2, P < 0.05. These findings suggest a familial component to childhood respiratory trouble which may have a hereditary basis.
Adolescent↗
Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates.
Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.
Acute Disease↗
From the mouths of babes....
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Child, Preschool↗
Respiratory syncytial virus-associated lower respiratory illnesses: possible influence of other agents. The Group Health Medical Associates.
Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Children's Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.
Child, Preschool↗
Exclusive breast-feeding for at least 4 months protects against otitis media.
OBJECTIVE: This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.
Acute Disease↗
Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life. Group Health Medical Associates.
BACKGROUND: Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed. METHODS: Information on day-care arrangements was elicited from 1006 parents of infants for five age intervals in the first 3 years of life: birth through 3 months, 4 to 6 months, 6 to 12 months, 1 to 2 years, and 2 to 3 years. Data on LRIs in the first 3 years of life were recorded by pediatricians at the time of the acute illnesses. RESULTS: After controlling for other risk factors, the presence of three or more unrelated children in the care setting was associated with significant risks of LRI of up to twofold or more from 4 months of age to 3 years. Type of care setting was not a significant risk factor during this time period. In the third year of life, the risk of wheezing LRI in the presence of a smoking caregiver was more than threefold for those in another residential home setting. No significant protective effect against LRIs in the third year of life associated with longer prior day-care enrollment was demonstrated. CONCLUSION: The presence of three or more unrelated children in the care setting and the presence of a smoking caregiver were significant independent risk factors for LRIs during the first 3 years of life. Prolonged day-care did not protect against LRIs in the third year of life.
Caregivers↗
Maternal age as a risk factor for wheezing lower respiratory illnesses in the first year of life.
Postneonatal mortality due to respiratory illnesses is known to be inversely related to maternal age, but the possible role of young motherhood as a risk factor for respiratory morbidity in infants has not been thoroughly explored. The authors studied the incidence of lower respiratory tract illnesses during the first year of life, as ascertained by health plan pediatricians, in over 1,200 infants enrolled at birth between 1980 and 1984 in Tucson, Arizona. The incidence of wheezing lower respiratory tract illnesses increased significantly (p = 0.005) with decreasing maternal age, whereas the incidence of nonwheezing lower respiratory tract illness was independent of maternal age. A logistic regression was used to control for the effects of several known confounding factors. When compared with infants of mothers aged more than 30 years, adjusted odds ratios were 2.4 (95% confidence interval 1.8-3.1) for infants whose mothers were less than age 21 years (p < 0.0001), 1.8 (95% confidence interval 1.4-2.3) for infants whose mothers were aged 21-25 (p < 0.0001); and 1.4 (95% confidence interval 1.1-1.6) for infants whose mothers were aged 26-30 (p < 0.001). These results suggest that young motherhood is an important risk factor for wheezing lower respiratory tract illnesses during the first year of life. Both biological and social factors related to maternal age may explain these findings.
Adult↗
The clinical spectrum of chronic appendiceal abscess in cystic fibrosis.
OBJECTIVE: To describe the varied characteristics seen in patients with cystic fibrosis who develop chronic abscess formation secondary to unrecognized appendicitis. DESIGN: Patient series. SETTING: Cystic Fibrosis Care Centers in Columbus, Ohio, and Tucson, Ariz. PARTICIPANTS: Five patients with cystic fibrosis who developed chronic abdominal abscesses secondary to occult appendicitis are described. Two patients developed fistula formation with purulent fluid drainage before diagnosis. One patient developed an extensive psoas abscess. Another presented with prolonged fever of unknown origin. These patients were identified by retrospective review of the past 20-year experience at two Cystic Fibrosis Care Centers. CONCLUSIONS: Development of chronic abdominal abscess related to unrecognized appendicitis is a rare but important complication in patients with cystic fibrosis. Prompt diagnosis depends on physician familiarity with the varied presentations of this entity. Diagnostic abdominal computed tomography and/or ultrasonography should particularly be considered when patients with cystic fibrosis present with pain, mass, or drainage from the right flank; prolonged fever; a limp; or failure of suspected meconium ileus equivalent syndrome to respond promptly to cathartic measures.
Abscess↗