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Background: Postural drainage chest physiotherapy in infants with cystic fibrosis (CF) exacerbates gastro-oesophageal reflux (GOR) and may contribute to a more rapid deterioration in lung function., Aims: To compare standard postural drainage chest physiotherapy (SPT) and a modified physiotherapy regimen (MPT) without head-down tilt, with regard to GOR, arousal state, and cardiorespiratory function., Methods: Twenty infants with CF underwent 30 hour oesophageal pH monitoring, during which four chest physiotherapy sessions were administered (day 1: MPT-SPT; day 2: SPT-MPT). Arousal state, heart rate, and oxygen saturation were documented for each of the physiotherapy positions (supine, prone, right lateral, and left lateral with (SPT) or without (MPT) 30 degrees head-down tilt)., Results: Significantly more reflux episodes occurred during SPT than during MPT, but there were no significant differences in median episode duration or fractional reflux time. During SPT, left lateral positioning was associated with fewer reflux episodes compared to other positions. During supine and prone positioning, more reflux episodes occurred during SPT than during MPT. Infants were significantly more likely to be awake or cry during SPT. There was a significant association between crying and reflux episodes for SPT. Non-nutritive sucking was associated with a significant reduction in reflux episodes during SPT. Oxygen saturation during SPT was significantly lower during crying and other waking, and non-nutritive sucking during SPT was associated with a significant increase in oxygen saturation., Conclusions: SPT is associated with GOR, distressed behaviour, and lower oxygen saturation.

There is controversy about the need for postural drainage physiotherapy in asymptomatic infants with cystic fibrosis (CF). We aimed to compare the effectiveness of standard postural drainage chest physiotherapy (SPT) with a modified physiotherapy regimen without head-down tilt (MPT) in young infants with CF. Twenty newly diagnosed infants with CF (mean age, 2.1 months; range, 1-4) were randomized to SPT or MPT. Parents kept a detailed symptom and treatment diary for the following 12 months. Serial chest radiographs, taken at diagnosis, 12 months, 2(1/2) years, and 5 years after diagnosis, were assessed using the Brasfield score. Pulmonary function tests were compared between groups after 5 years. Of the 20 infants, 16 (80%) completed the review at 12 months, and 14 (70%) at 2(1/2) and 5 years. Patients receiving SPT had more days with upper respiratory tract symptoms than those on MPT (70 +/- 32.8 vs. 37 +/- 24.9 days; P = 0.04) and required longer courses of antibiotics (23 +/- 28.5 vs. 14 +/- 11.2 days; P = 0.05). Chest x-ray scores were similar at diagnosis but were worse at 2(1/2) years for those receiving SPT (P = 0.03). Forced vital capacity and forced expired volume in 1 sec (FEV(1)) at 5-6 years was lower for SPT than for MPT (P < 0.05). In conclusion, MPT was associated with fewer respiratory complications than SPT in infants with CF., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To determine whether a defect in energy metabolism exists in infants with cystic fibrosis (CF)., Design: Unselected, newly-diagnosed subjects with CF (n = 46) and 24 healthy infants aged <20 weeks had measurements of resting energy expenditure (REE), total energy expenditure (TEE) (n = 25), and body composition. Metabolizable energy intake (MEI) was calculated. Genotype, energy intake, and pancreatic status was determined in all subjects with CF, and 24 underwent bronchial lavage., Results: At diagnosis, infants with CF detected by newborn screening had significant anthropometric deficits (mean [SD] z-weight = 0.5 [1.0], z-length = 0.7 [1.3]) associated with pancreatic insufficiency. Their REE, TEE, or MEI (absolute measurements, per unit body weight or fat-free mass) were not increased. No relationship between REE, TEE, or MEI and Delta F(508) genotype, and no proportional differences in individual components of MEI between subjects with CF and controls, or between subjects with CF who were homozygotes or compound heterozygotes for Delta F(508) were observed. REE and TEE were not correlated with bronchial infection or inflammation., Conclusion: Growth impairment during the first weeks of life in infants with CF is associated with pancreatic insufficiency. However, there is no evidence for a defect of energy metabolism related to Delta F(508), and in infants with CF, minimal lung disease is unaccompanied by increased energy expenditure.

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.

Limited data in children with cystic fibrosis (CF) suggest that respiratory viral infections during infancy result in substantial morbidity. Eighty of 101 (79%) infants with CF diagnosed by neonatal screening during 1991-1996 were recruited into a prospective, multiple-birth cohort study. We aimed to perform an initial, then annual bronchoalveolar lavage (BAL) for bacterial and viral culture, cytology, IL-8, and elastolytic activity over the following 2 years. When possible, BAL was also performed during any hospitalization for a pulmonary exacerbation, and additional specimens for viral culture were collected by nasopharyngeal aspiration. Thirteen infants undergoing bronchoscopy for congenital stridor served as disease controls. During infancy, 31 children (39%) were hospitalized for respiratory disease and 20 (65%) cases had an etiologic agent identified. Respiratory viruses were detected in 16/31 (52%) cases, including four with simultaneous bacterial infection. Another four were infected with Staphylococcus aureus. Respiratory syncytial virus predominated and was found in seven infants. In the absence of bacteria, those with viral infections had acute onset of respiratory distress, were not treated with antibiotics, and had an uncomplicated hospital course. Compared to noninfected CF subjects and controls, infected infants had elevated BAL inflammatory indices (P < 0.01). Eleven of 31 (35%) hospitalized infants followed for 12-60 months acquired Pseudomonas aeruginosa, compared with only three of 49 (6%) subjects not hospitalized for respiratory symptoms during infancy (risk ratio 5.8, CI 1.9, 24). We conclude that respiratory viruses are important causes of hospitalization in CF infants. While viral infections were self-limited, they were accompanied by airway inflammatory changes, and admission to hospital was associated with early acquisition of Pseudomonas aeruginosa and persistent respiratory symptoms.

Objectives: To determine the clinical effects of a change from postural drainage (PD) to positive expiratory pressure chest physiotherapy (PEP) in children with cystic fibrosis (CF) and symptoms of gastro-oesophageal reflux (GOR). To measure the effects of PD on GOR in children with CF., Methods: Study 1: Six adolescents with CF and symptoms of GOR during PD were changed to upright PEP physiotherapy. The effects on lung function, reflux symptom scores and annual hospital days were measured. Study 2: Twenty-four children with CF (mean age 11 years) and symptoms suggestive of GOR underwent 24-h pH monitoring, including periods of chest physiotherapy., Results: Study 1: All six patients reported a reduction in reflux symptoms during PEP therapy (P < 0.001). Lung function parameters improved during the first 6 months of PEP (P < 0.001). This improvement was sustained for a further 18 months. Annual hospital days decreased significantly (P < 0.0005). Study 2: Nine of 24 patients (37.5%) had pathological GOR. Reflux episodes were significantly increased during PD (P < 0.0001), as was fractional reflux time (P < 0.01)., Conclusions: Upright PEP physiotherapy may be more appropriate than PD in selected patients with CF and symptomatic GOR. The role of GOR as a cofactor in the progression of pulmonary disease in CF needs further evaluation.

Aim: To establish the incidence of pathological gastro-oesophageal reflux (GOR) in newly diagnosed infants with cystic fibrosis and to identify clinical predictors of increased reflux., Methods: 26 infants with cystic fibrosis less than 6 months of age (14 male, 12 female; mean (SEM) age 2.1 (0.21) months, range 0.8 to 5.6 months) underwent prolonged oesophageal pH monitoring (mean duration 27.1 (0.49) hours; range 21.3 to 30.2 hours). Reflux symptoms, anthropometric variables, pancreatic status, meconium ileus, genotype, and chest x ray findings were correlated with pH monitoring data., Results: Five infants (19.2%) had an abnormal fractional reflux time of greater than 10%, seven (26.9%) of 5-10%, and 14 (53.8%) of below 5%. Infants who presented with frequent vomiting had a significantly higher fractional reflux time than infants who had infrequent or no vomiting. There was no significant association between abnormal chest x rays and pathological GOR. Sex, genotype, nutritional status, meconium ileus, and pancreatic enzyme supplementation were not significantly associated with pathological GOR., Conclusions: About one in five newly diagnosed infants with cystic fibrosis had pathological GOR. Pathologically increased reflux was present before radiological lung disease was established. Apart from frequent vomiting, no useful clinical predictors of pathological reflux were found.

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program. These infants were divided into three groups: 10 had not experienced respiratory symptoms or received antibiotics and pathogens were absent in their BAL fluid; 18 had clear evidence of lower respiratory viral or bacterial (> or = 10(5) CFU/ml) infection; and the remaining 18 had either respiratory symptoms, taken antibiotics, or had < 10(5) CFU/ml of respiratory pathogens. Their BAL cytology, interleukin-8, and elastolytic activity were compared with those from 13 control subjects. In a longitudinal study to assess if inflammation develops or persists in the absence of infection, the results of 56 paired annual BAL specimens from 44 CF infants were grouped according to whether they showed absence, development, clearance, or persistence of infection. In newly diagnosed infants with CF, those without infection had BAL profiles comparable with control subjects while those with a lower respiratory infection had evidence of airway inflammation. In older children, the development and persistence of infection was accompanied by increased inflammatory markers, whereas these were decreased in the absence, or with the clearance, of infection. We conclude that airway inflammation follows respiratory infection and, in young children, improves when pathogens are eradicated from the airways.

In adults, cough sensitivity is influenced by gender and is heightened in those with non-productive cough. This study examined if cough sensitivity is (i) altered in children with asthma, recurrent cough, and cystic fibrosis and (ii) influenced by age, gender, or forced expiratory volume in one second (FEV1). Cough sensitivity to capsaicin and spirometry were performed on 209 children grouped by the diagnosis of asthma, recurrent dry cough, cystic fibrosis, and controls. Cough sensitivity was increased in children with recurrent cough, and lower in children with cystic fibrosis when compared with children with asthma and controls. Age influenced cough sensitivity in the controls. In the asthmatics, FEV1 (% predicted) correlated to cough sensitivity measures. There was no gender difference in cough sensitivity. It is concluded that cough sensitivity is different among children with recurrent dry cough, asthma, and cystic fibrosis. In children, age, but not gender, influences cough sensitivity measures and when cough sensitivity is used in comparative studies, children should be matched for age and FEV1.

Unlabelled: Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function., Aim: To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastroesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT)., Method: Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days., Results: The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%) p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time., Conclusions: SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.

As collections of lower respiratory tract specimens from young children with cystic fibrosis (CF) are difficult, we determined whether oropharyngeal cultures predicted lower airway pathogens. During 1992-1994, 75 of 90 (83%) infants with CF diagnosed by neonatal screening had 150 simultaneous bronchoalveolar lavage (BAL) and oropharyngeal specimens collected for quantitative bacterial culture at a mean age of 17 months (range, 1-52). Ten children undergoing bronchoscopy for stridor served as controls. Total and differential cell counts and interleukin-8 concentrations were measured in BAL fluid. A subset of bacterial pathogens were typed by pulsed field gel electrophoresis. A non-linear relationship with inflammatory markers supported a diagnosis of lower airway infection when > or = 10(5) colony-forming units/ml were detected. This criterion was met in 47 (31%) BAL cultures from 37 (49%) children. Staphylococcus aureus (19%), Pseudomonas aeruginosa (11%), and Hemophilus influenzae (8%) were the major lower airway pathogens. In oropharyngeal cultures, S. aureus (47%), Escherichia coli (23%), H. influenzae (15%), and P. aeruginosa (13%) predominated. The sensitivity, specificity, and positive and negative predictive values of oropharyngeal cultures for pathogens causing lower respiratory infections were 82%, 83%, 41%, and 97%, respectively. When there was agreement between paired oropharyngeal and BAL cultures, genetic fingerprinting showed some strains of the same organism were unrelated. We conclude that oropharyngeal cultures do not reliably predict the presence of bacterial pathogens in the lower airways of young CF children.

Purpose: The improved life-expectancy in cystic fibrosis (CF) results in the fact that the majority of affected young women now survive to face the same reproductive health decisions as other women, in addition to those that specifically relate to CF. The aim of this study was to assess the reproductive health knowledge of women with CF, to investigate the range of their reproductive health problems, and to review their reproductive health attitudes and behaviors., Methods: Women aged 18 years and over attending CF services in the state of Victoria, Australia were invited to complete a reproductive health questionnaire. Comparison subjects (n = 76) were enrolled from 2 primary care practices., Results: Fifty-five women participated (89%), with a median age of 22 years (range 18-50). There was no significant difference in marital status between the two groups and a similar proportion were sexually active, yet women with CF were less likely to use contraception. A majority of women with CF believed that fertility was reduced, and there was poor knowledge of the potentially deleterious effect of pregnancy. A relatively high proportion were planning to become pregnant in the near future. Twenty-two percent had tried to conceive, with a success rate of 67%., Conclusions: Women with CF are currently lacking important information about reproductive health that potentially has a major impact on their health and their lives.

Purpose: The changing expectations, therapies and outcomes for young people with cystic fibrosis (CF) necessitate a re-evaluation of the impact of this chronic illness on adolescent development. The aim of this study was to assess the psychological well-being and adjustment of contemporary adolescents with CF., Methods: Forty-nine adolescents with CF (24 males, 25 females) aged 14-18 years were enrolled from the Royal Children's Hospital CF Clinic, Melbourne, Australia. The Offer Self-Image Questionnaire was administered to participating subjects whose growth and pubertal developmental and pulmonary function was assessed., Results: The mean (SD) FEV1% was 82 (21), and mean (SD) National Institute of Health clinical score was 81 (12). There were no significant differences between males and females in pulmonary function or clinical scores, but growth and pubertal development were delayed in both sexes. Females, but not males, with CF were less well-adjusted than their healthy peers. Two-way analysis of variance was performed and showed significant sex differences in sub-scales of the Offer questionnaire numbers I, II, III, VI, VIII, IX, as well as in the total score. Age was significant only for scales II and VIII, and only scale II displayed an interaction between sex and age., Conclusions: This study suggests that adjustment and self-esteem are less than ideal in young people with CF, especially females.

The aim of this study was to define the within-subject variability for tests of respiratory function in patients with cystic fibrosis (CF) within the day, from day to day and from week to week. Twenty-eight patients with CF (aged 9-19 years) and 23 healthy height matched controls (aged 9-18 years) had measurements made of spirometry, lung volumes, maximal flows at three lung volumes and maximal inspiratory and expiratory pressures at the mouth. Testings were done on nine occasions, three times within a day, on consecutive days at one week intervals. Each individual's variability was summarized both as the within-subject coefficient of variation (WCV) and within-subject standard deviation (WSD). Means of WSD and median WCV are reported for both the patients with CF and normal subjects. The within-subject variability of VC, FEV1, TLC, RV, and RV/TLC was more appropriately assessed by the use of WSD rather than WCV. The WSDs in the CF group were significantly more variable (P less than 0.005) than in the normals for VC and FEV1. WCV best summarized within-subject variation for FEF25-75, FRC, V25, V50max and V75max for which the CF subjects were significantly more variable (P less than 0.005). Individuals' variability was very consistent, therefore assessment of significant change could be made more accurately by predetermining the variability of that individual, rather than using group data. We stress the importance to consider increased variability from day to day and week to week in the interpretation of change in lung function in patients with CF, and provide reference values for accurate interpretation of serial pulmonary function test results.

Cystic fibrosis was present in 35 of 5,265 first cousins of index cases with the disease. The gene frequency was estimated to be .0281 +/- .00544, using an improved method that allows for the influence of cousin sibship size upon the estimate. This figure is higher than that obtained by direct counting of cases in Victoria, Australia, from 1955-1979 (.0198 +/- .000127), raising the possibility that multiple gene loci may be involved in this disease. Further analysis showed that the number of affected first cousins fitted very well with an expected number based on a model involving two gene loci, each responsible for half the cases of cystic fibrosis. Agreement with expectations based on a single locus was not good. An alternate explanation of gross underascertainment of cases is dismissed because the index sibships were shown to fit very closely a truncate binomial distribution. The gene frequencies at the putative two loci would then each be .0140 and heterozygote frequencies one in 36. One in 18 people would be heterozygous at either one or the other of the loci.

One hundred and twenty-eight patients managed by, or in association with, the Cystic Fibrosis Clinic, Royal Children's Hospital, Melbourne, have reached the age of 16 years; and 83 patients were alive on December 31, 1978, the oldest being 65 years of age. Survival data analysis on this group of patients showed a cumulative survival of 49% to 28 years. Despite the presence of substantial lung disease, most patients continued in full-time employment or education, and enjoyed a normal range of social activities. A review of these adults justifies a positive approach to the management of all patients with cystic fibrosis. With an increasing proportion of patients reaching adult life with minimal lung disease, the outlook can be expected to improve further over the next decade.

A study of 29 children and adolescents with cystic fibrosis over 2 years showed some evidence of benefit from the twice daily inhalation of 20 mg nebulized gentamicin when compared to the inhalation of a nebulized saline mixture. Clinical symptoms, deterioration in pulmonary function, antibiotic usage, days in hospital and development of Pseudomonas aeruginosa in the sputum were recorded. There was no significant difference in antibiotic usage, days in hospital or clinical symptoms between the two regimes. Those subjects with P. aeruginosa in sputum showed significantly less deterioration in lung function over 2 years while using gentamicin aerosol. There was no difference in progress between the two treatment regimes for those subjects with P. aeruginosa in sputum at the beginning of the study, nor was there any difference in the number developing P. aeruginosa in sputum.

The incidence of cystic fibrosis among the Australian born children of parents born in Italy was 1:3 625 live births and among Australian born children of parents born in Greece 1:3 726. These incidences were significantly lower than the incidence for cystic fibrosis of 1:2 021 in children born to Australian born parents, about 90% of whom have ancestors born in the British Isles. The figures suggest there are significant variations in the incidence of cystic fibrosis in different European populations.

A child with cystic fibrosis and asthma developed pulmonary candidiasis. Predisposing factors in this patient were prolonged antibiotic therapy, high-dose corticosteroids, and intravenous catherisation. A diagnosis was made by lung puncture and confirmed by rapid response to 5-fluorocytosine.

Data on 622 patients with cystic fibrosis born in Victoria, Australia from 1955 to 1980 and on 344 surviving patients in the care of a specialist clinic on June 30, 1983 were analyzed for factors associated with better survival and a less rapid progress of lung disease. Presentation with predominantly gastrointestinal symptoms, other than meconium ileus, was associated with an improved prognosis, whereas presentation with predominantly respiratory symptoms was associated with a worse prognosis. While infants diagnosed before the age of 6 months as a result of routine testing because of a family history of the disease seemed to have less rapid progress of lung disease, their ultimate survival did not seem to be better than that of patients presenting symptomatically after the newborn period. The sex of the patients did not appear to have prognostic significance. Age at diagnosis did not affect rate of progress of lung disease or survival when infants dying within 6 months of birth were excluded. There was a close association between the extent of lung disease at diagnosis and current lung disease. Failure to reverse extensive disease at diagnosis or deterioration of lung disease in the first year after diagnosis was associated with a less favourable course.

The survival of 320 patients, who were born in and after 1958 with cystic fibrosis and managed by the Departments of Thoracic Medicine and Gastroenterology, Royal Children's Hospital, Melbourne, is reviewed. Eighty per cent of patients survived to 11 years of age, and 64% to 18 years. Of patients managed between 1973 and 1977, 91% survived to 12 years of age, and 80% to 17 years of age. In the same period, 79% of patients survived for 16 years after diagnosis. Forty-four per cent of the 240 patients currently being managed have no significant permanent lung disease, and only 9% have advanced disease.

The importance of bronchial hyper-reactivity and allergy, and treatment with bronchodilators and corticosteroids, in the management of patients with cystic fibrosis is poorly understood. Three tests generally regarded as useful in the diagnosis of asthma were evaluated in 25 children with cystic fibrosis. The constancy of a child's response was assessed by histamine bronchial provocation, exercise challenge, and tests of skin allergy during a 6-month period. Although a positive response to these tests was related to impaired pulmonary function, 44% of children had variable responses to histamine, 56% to exercise, and 24% to skin tests which were unrelated to exacerbations of chest infection or to changes in pulmonary function. These results show the complex nature of airways hyper-reactivity and allergy in cystic fibrosis, and suggest that 'anti-asthma' therapy is not justified solely on the basis of one positive response to these tests.

In a material of 22 Danish, 26 Canadian, 10 Australian, 5 English and 5 American families with at least 2 children affected with cystic fibrosis (CF) a combined positive LOD score of 3.46 was found for the relationship cystic fibrosis-paraoxonase (PON) at recombination fraction theta = 0.07 in males and theta = 0.13 in females. Assuming a three allele model for PON the LOD score was 4.50 at the same recombination fractions. This confirms our earlier finding of an indication of CF-PON synteny.

We attempted to measure the distribution of ventilation in 24 children who had cystic fibrosis (CF) and 58 control subjects (ages 3.9-6.8 years) using the multiple breath nitrogen washout (MBNW) test. Moment analysis was performed on the MBNW curve, and the first and second moment ratios were derived. Only 40 (49%) of the children were able to complete the test satisfactorily and success was related to age (P less than 0.01). Children who had CF had higher moment ratios, both first and second, than did controls (P less than 0.001); also, CF subjects who had more severe symptoms had higher moment ratios than did those who had minimal symptoms (P less than 0.005). The first moment ratio had a lower coefficient of variation than did the second (14% vs 31%) and, in 8 children who performed the test in duplicate, it also had a lower index of intrasubject variability (6.4% vs 15.1%). Both ratios were lower than those described in older children and in adults, which is consistent with the more rapid washout seen in this age group. Although moment analysis of the MBNW curve can be performed in approximately 50% of children 4 to 6-years-old, the complexity of the test, the apparatus, and the analysis and the high failure rate in children under the age of 6 are likely to restrict its use to research studies in specialized pediatric respiratory laboratories.

There has been a major change in the outlook for children with cystic fibrosis during the last 20 years. Provided the diagnosis is made before serious irreversible lung disease has occurred, most patients can expect to reach adult life without very serious disability.