Cystic fibrosis: decreased conjugation and excretion of [14C]spermidine.

Free and conjugated [14C]spermidine were measured in plasma samples from normal individuals and cystic fibrosis patients. Within 4 minutes, the 14C-labeled material in the plasma from normal individuals was 70 percent conjugated compared to no detectable conjugation by cystic fibrosis patients. Further, the patients excreted only 11 to 13 percent of the [14C]spermidine in their urine within 72 hours whereas normal excretion was 60 to 76 percent. In both cases, the labeled material was in a conjugated form.

Hypoelectrolytemia and metabolic alkalosis in infants with cystic fibrosis.

The records of all children in the Tucson area diagnosed as having cystic fibrosis (CF) before the age of 12 months were reviewed to ascertain the prevalence of metabolic alkalosis as a major presenting manifestation of CF. Five of eleven infants (46%) in whom CF had been diagnosed between 1 and 12 months of age initially were seen with hypokalemia, hypochloremia, and metabolic alkalosis unassociated with marked dehydration, hyperpyrexia, or major pulmonary and/or gastrointestinal symptoms. Two infants had repeated episodes of metabolic alkalosis; for one of these infants, both episodes of metabolic alkalosis occurred before the diagnosis of CF. It is postulated that chronic loss of sweat electrolytes together with mild gastrointestinal or respiratory illness may predispose the infant with cystic fibrosis to a severe electrolyte and acid-base disturbance. The lack of shock and hyperpyrexia together with the apparent chronicity of electrolyte losses differentiates metabolic alkalosis from the heat prostration syndrome, a more acute complication of cystic fibrosis. Quantitative sweat testing should be part of the evaluation of any infant with unexplained metabolic alkalosis. Serum electrolytes should be assessed regularly in infants with cystic fibrosis during hot weather months.

Family history of asthma in infants with bronchopulmonary dysplasia.

The role of genetic or familial factors in the development of bronchopulmonary dysplasia (BPD) has not been evaluated. Detailed histories concerning asthma, allergy, and other lung diseases were obtained on first and second degree relatives of 17 infants with BPD, and 21 infants who had hyaline membrane disease but who did not develop BPD (HMD group). All infants in the BPD and HMD groups had hyaline membrane disease requiring assisted ventilation and greater than 50% inspired oxygen in the first five days of life. The diagnosis of HMD and BPD were made on radiographic and clinical criteria. Of the 17 infants with BPD, 13 had first or second degree relatives with physician-diagnosed asthma, compared to seven of 21 in the HMD group (P less than .01). In addition, a significantly greater number of relatives of BPD infants (P less than .005) had been hospitalized for their asthma as compared to HMD relatives. There were no differences between the groups for allergic rhinitis, eczema, bronchitis, emphysema, chronic cough, smoking, or wheezing with respiratory illnesses. These results suggest the possibility that airways with a genetic predisposition for reactivity may become highly reactive following neonatal lung disorders and their treatment. These irritable airways may then contribute to the development, or progression, or both of BPD.

Infant-feeding practices among middle-class Anglos and Hispanics.

Feeding practices have been analyzed prospectively in a sample of 1,112 healthy infants selected from families using an HMO. Data were collected at well-child visits during the first year of life regarding breast-feeding, formula feeding, and use of solid foods and cow's milk. Seventy percent of all infants were breast-fed, with the mean duration of breast-feeding being almost 7 months. Factors positively associated with breast-feeding included education and marriage, whereas maternal employment outside the home and ethnicity (being Hispanic rather than Anglo-American) were related to bottle feeding. Solid foods were introduced earlier by Hispanics and, also, among less well educated and single women; maternal employment was unrelated to the introduction of solid foods. Multiple regression analysis indicated different patterns for the two ethnic groups: education and employment were related to almost all feeding practices for Anglo-Americans, whereas education and employment predicted few feeding practices for the Hispanics. These findings suggest that the effects of ethnicity are independent of those of education.

Chronic bronchitis in childhood: what is it?

According to national statistics, over 2.5 million children have chronic bronchitis (CB). The characteristics of childhood CB and the similarities to the adult form are unknown. To determine the conditions under which childhood CB is diagnosed and to evaluate how it is treated, questionnaires were sent to 103 pediatricians and family physicians to Tucson. Forty-five percent responded. A chronic productive cough lasting at least three months a year was important for the diagnosis of CB for only 55% of pediatricians and 74% of family physicians. Recurrent episodes of cough lasting more than two weeks were important for the diagnosis of CB for 86% pediatricians. Sputum production was important for the diagnosis for about 50% of physicians felt that allergies were a common cause of childhood CB and bronchodilators were commonly used to treat CB. The results of this survey suggest that: (1) the diagnosis of CB in childhood is not often based on the usual epidemiologic criteria used for diagnosing CB in adults; and (2) CB in childhood may have considerable overlap with asthma with respect to etiology, pathophysiology, and treatment. In fact, for many children, there appear to be few ways to distinguish asthma from CB.

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.

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.

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.

Flow-volume curves in infants with lung disease.

Partial expiratory flow-volume maneuvers have been performed on nine occasions on six infants with a variety of pulmonary problems using a new technique for thoracic compression. The infants were placed within an inflatable bag that was, itself, within a canvas bag. By sudden controlled inflation of the inner bag at end inspiration, partial expiratory flow-volume curves were generated and recorded by means of a face mask and pneumotachograph. By comparing these flow results with those airway resistance and lung volume measurements obtained from the infants in whole body plethysmography and by noting the effect of inhaling a helium/oxygen gas mixture, it was possible to partition the airway obstruction between large and small airways. The presence of small airway obstruction was noted in the absence of changes in airway resistance or lung volume in several instances. A complete evaluation of airway function should include this test of forced expiration for greater understanding and treatment of lung disease in infancy.

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.

The relationship between flow transients and bronchial lability in cystic fibrosis.

Patients with cystic fibrosis (CF), in contrast to asthmatic subjects, often show a larger increase than decrease (bronchial lability) in peak flows following exercise. Children with CF also often have large supramaximal expiratory flow transients, produced by rapid expulsion of air from conducting airways that are being dynamically compressed. We studied the relationship between bronchial lability and flow transients to explain the peculiar form of bronchial lability found in certain CF patients. At baseline, six of seven CF patients had flow transients, suggestive of decreased resting tone of the conducting airways. Following exercise, there was a strong positive correlation (r = 0.76, P less than .01) between changes in peak flow and changes in the volume of the flow transients. Four subjects increased both, two did not change either, and in one subject both peak flow and the volume of the flow transient decreased. This study suggests that the unique, previously unexplained form of postexercise bronchial lability observed in some CF patients is probably due mainly to flow transients that contribute to peak flows. These transients are probably related to increased compliance of the conducting airways in this disease.

Unusual abnormalities in adolescent siblings with alpha 1-antitrypsin deficiency.

We studied, over a four-year period, two adolescents with alpha 1-antitrypsin (AAT) deficiency who subsequently died from complications of hepatic cirrhosis. Serial pulmonary function studies indicated mild obstructive lung disease involving peripheral airways in both patients. Postmortem histologic and pulmonary morphometric studies indicated mild diffuse airspace and bronchial gland enlargement, and slight dilation of small airways. This airspace enlargement may represent the early stage of lung disease in AAT-deficient subjects and suggests that pulmonary anatomic changes may occur long before the onset of clinically and pathologically significant emphysema.

A descriptive analysis of the growth and decline of the FVC and FEV1.

Using data obtained during the first four complete surveys of a general population sample (2,435 spirometric studies on 916 different asymptomatic nonsmoking subjects), we have derived mathematically continuous equations designed to describe the stages of growth, maturation, and subsequent decline in the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). With this type of analysis, there appears to be a period from late childhood through adolescence in which maturation significantly increases FVC and FEV1 independent of growth, and a stage from late adolescence to the early or mid-30s in which there is relatively little change in these measurements. Progressive decline in FVC and FEV1 may not actually begin until the mid-30s. The mathematical formulae presented here were derived in a manner intended to describe biologic events and are not intended for use as prediction equations. The FEV1/FVC ratio appeared to be primarily a function of the FVC itself in young subjects. After the age of 33 years, FEV1/FVC also decreased with age, independent of the size of the FVC.

Echocardiographic profiles of the long-term cardiac changes in cystic fibrosis.

In this echocardiographic study, assessment of the heart in children with cystic fibrosis has shown that changes occur in not only the right ventricle but also in the left ventricle and aorta, as compared with normal. Echocardiograms could be successfully performed in 34 of 37 patients. The thickness of the right ventricular anterior wall and the dimension of the right ventricular cavity were abnormal, even in patients with mild disease (National Institutes of Health [NIH] score for severity of disease of 85 or greater). Larger, older children with lower NIH score had disproportionately larger right ventricular anterior walls and cavities. The thickness of the septal wall, the thickness of the left ventricular posterior wall, and the aortic dimensions were increased in those with severe disease. The dimensions of the left ventricular cavity for the population were slightly but significantly smaller than normal in systole and in diastole throughout the course of the disease. This study demonstrates that echocardiography is an effective noninvasive means of assessing the long-term changes in children with cystic fibrosis. These changes occur in both sides of the heart and appear to worsen as the disease progresses.

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.

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.

Relationship of infant feeding to recurrent wheezing at age 6 years.

OBJECTIVES: To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses. DESIGN: Prospective, longitudinal study of healthy infants followed up from birth to 6 years of age. SETTING: Nonselected health maintenance organization population in Tucson, Arizona. PARTICIPANTS: There were 1246 healthy infants enrolled at birth, 988 of whom had data on both infant feeding and wheezing at age 6 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recurrent wheeze (four or more episodes in the past year) was assessed by a questionnaire that was completed by parents when the children were 6 years old. Children were classified by atopic status on the basis of skin prick tests. RESULTS: Breast-feeding information was collected prospectively, and lower respiratory tract illnesses in the first 3 years of life were diagnosed by the pediatrician. Being breast-fed was associated with lower rates of recurrent wheeze at age 6 years (3.1% vs 9.7%, P < .01) for nonatopic children; this relationship was not significant for atopic children. The relationship of breast-feeding with recurrent wheeze was apparent among nonatopic children both with and without a wheezing lower respiratory tract illness in the first 6 months of life. When potential confounders, including early wheezing lower respiratory tract illness, were included in a multivariate model, nonatopic children who had not been breast-fed had three times the odds of wheezing recurrently (odds ratio, 3.03; confidence interval, 1.06 to 8.69). Eleven percent of recurrent wheeze among nonatopic children could be attributed to not breast-feeding. CONCLUSIONS: Recurrent wheeze at age 6 years is less common among nonatopic children who were breast-fed as infants. This effect is independent of whether the child wheezed with a lower respiratory tract illness in the first 6 months of life.

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.

Infants with upper respiratory illnesses have significant reductions in maximal expiratory flow.

We studied maximal expiratory flows at functional residual capacity (VmaxFRC) obtained by use of the chest compression technique in 9 infants who had signs of upper respiratory illness (URI) at the time of testing, and in 9 infants who were symptom-free but whose parents reported they had a URI in the previous month. When compared to 109 infants with no URI, infants with current URI had 40% lower VmaxFRC (mean +/- SD: 125.7 +/- 54.5 mL/s vs. 73.6 +/- 53.6 mL/s; P less than 0.01). Infants with a past URI had mean values for VmaxFRC (120.2 +/- 50.2 mL/s) that were not significantly different from those of infants with no URI. Changes in the shape of the flow-volume loop analogous to those reported in infants with lower airway obstruction were also noticed in infants with current URI. These findings suggest that, as in older children and adults, clinically unapparent alterations in lower airway function occur during URI in infants.

Airway responsiveness to cold, dry air in normal infants.

Reactive airway disease may be related to genetic, infectious, and environmental factors. The latter two have been well documented, but there are no data on nonspecific airway responsiveness in normal infants prior to any insult to the respiratory tract. We measured forced expiratory flow by the thoracic compression technique and lung volume in 30 normal infants before and after challenge with cold, dry air (CDA) and compared the results with those in 12 infants who did not receive CDA challenge. As a group, infants challenged with CDA had a mean decrease in VmaxFRC of 17.9 +/- 24.1% SD. This was significantly different (P less than 0.01) from the lack of change (+ 1.3 +/- 18.1% SD) seen in the control group. We conclude that nonspecific airway reactivity may exist from early infancy and may predate any known lung injury. The relationship of this airway responsiveness to subsequent reactive airway disease and other respiratory illnesses is unknown and requires longitudinal study.