Macrolides for the long-term management of asthma--a meta-analysis of randomized clinical trials.

BACKGROUND: Macrolide antibiotics, which have anti-inflammatory and immune modulatory effects, have been studied as adjuncts for the management of asthma. However, results have been contradictory and trials underpowered. We therefore sought to conduct a meta-analysis of randomized controlled trials (RCT). METHODS: All RCT of prolonged macrolides (3+ weeks) for asthma treatment, published up to January 2013 in MEDLINE, Scopus, CINAHL, Highwire, and The Cochrane Collaboration Library, were included. Fixed- or random-effects models were used to calculate pooled weighted or standard mean differences (WMD or SMD, respectively). RESULTS: A total of 12 studies were included for analysis. The pooled effect of macrolides on FEV1 (eight trials, 381 subjects) was not significant (SMD 0.05, 95% CI -0.14-0.25), but there was a significant increase in peak expiratory flow (four trials, 419 subjects; WMD 6.7, 95% CI 1.35-12.06). Pooled analysis also showed significant improvements in symptom scores (eight studies, 478 subjects; WMD -0.46, 95% CI -0.60 to -0.32), quality of life (five trials, 346 subjects; WMD 0.18, 95% CI 0.001-0.37), and airway hyper-reactivity (two trials, 131 subjects; SMD 1.99, 95% CI 0.46-3.52). Post hoc evaluation showed limited statistical power to detect significant differences in FEV1. CONCLUSIONS: Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.

Necrotising pneumonia is an increasingly detected complication of pneumonia in children.

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period. A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up. A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993-1996, to 40 in the period 2001-2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, with Streptococcus pneumoniae as the predominant organism. Recently, other organisms, most notably methicillin-resistant Staphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation. Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia. Streptococcus pneumoniae remains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.

Vitamin A status in acute exacerbations of cystic fibrosis.

Vitamin A is an essential nutrient for epithelial cell maintenance and repair, and it is known that infectious stresses may depress plasma vitamin A concentrations. Patients with cystic fibrosis are at risk for vitamin A deficiency because of fat malabsorption as well as for the inflammatory stresses of pulmonary exacerbations of their underlying disease. We therefore hypothesized that acute pulmonary exacerbations of CF would depress plasma retinol concentrations, and that these concentrations would return to baseline values when clinical symptoms improved. We prospectively studied 35 CF patients (mean age: 24.2 y) consecutively admitted with pulmonary exacerbations. Plasma retinol, vitamin E, retinol binding protein (RBP), and C-reactive protein (CRP) concentrations were measured on hospital admission and discharge. Dietary intake was measured by using a semiquantitative food-frequency questionnaire. Regression analysis was used to identify significant clinical and laboratory correlates of retinol concentrations. On admission, mean (+/- SD) concentrations of plasma retinol were 1.14 +/- 0.5 mumol/L compared with 1.70 +/- 0.6 mumol/L on discharge (P = 0.0001). Of 35 subjects, 8 (22.9%) had plasma retinol concentrations considered to be in the deficient range (< 0.70 mumol/L). Concurrently, mean concentrations of plasma RBP increased during hospital admission (from 1.46 to 2.24 mumol/L, P = 0.003), and the mean CRP concentration declined (from 25.7 to 9.8 mg/L, P = 0.002). Significant positive correlations were found between plasma retinol concentrations at admission and age, weight, body mass index, triceps-skinfold-thickness percentile, midupper arm circumference percentile, plasma vitamin E, and RBP concentration, thus suggesting that better-nourished patients had more optimal vitamin A status. At admission, plasma retinol concentrations were negatively correlated with maximum body temperature and CRP concentrations, which indicated that the body's acute-phase response was associated with the depression in retinol concentrations. We conclude that plasma retinol concentrations are depressed in acute pulmonary exacerbations of cystic fibrosis, and that concentrations considered to be in the deficient range are common. Vitamin A metabolism during acute inflammatory stress deserves further study.

Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant.

A central hypoventilatory state developed in a 6-month-old boy with environmentally induced hyperthermia. The condition subsided within 24 hours of mechanical ventilation. Hypoxic and hypercapneic challenges performed 2 weeks later showed complete resolution of the respiratory chemoreceptor dysfunction. The damage to the CNS caused by accidental hyperthermia in general, and more specifically to the respiratory center, and its possible etiologic role in the pathophysiology of sudden infant death syndrome are discussed.

Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

OBJECTIVES: Using the large database from the Epidemiologic Study of Cystic Fibrosis (ESCF), the objectives of this study were to (1) estimate the reported prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF); (2) compare reported prevalence rates across geographic regions; (3) compare reported prevalence rates between patient subgroups based on demographic and disease characteristics; and (4) describe the ABPA group with regard to their sex, age, and disease severity. STUDY DESIGN: All patients > or = 5 years of age enrolled in ESCF between December 1993 and May 1996 were eligible. Criteria for the diagnosis of ABPA were defined by the ESCF guidelines. Prevalence rates for ABPA were calculated, and potential risk factors for the diagnosis of ABPA were analyzed, including sex, age, pulmonary function, diagnosis of asthma, presence of wheeze, and positive respiratory culture for Pseudomonas. RESULTS: There were 14,210 eligible patients enrolled in ESCF during this period, and ABPA was diagnosed in 281 patients (2%). Regional prevalence varied from 0.9% in the Southwest to 4.0% in the West. Increased prevalence rates occurred in female patients, the adolescent age group, and subjects with lower lung function, wheeze, asthma, and positive Pseudomonas cultures. Although most ABPA patients had evidence of airway obstruction, 10% had an FEV1 of > 100% of predicted. The rates of wheeze (17%) and asthma (30%) were lower than expected in the ABPA group. CONCLUSIONS: This observational study found a reported prevalence rate of ABPA of 2% of CF patients in a large database. This rate was lower than the 5 to 15% rate reported in smaller studies, suggesting that ABPA is underdiagnosed in the CF population. There was wide regional variation in reported prevalence rates, which is unexplained at this time. The characteristics of the patients with ABPA and the epidemiologic risk factors for diagnosis of ABPA were described. Simplified diagnostic criteria were adapted for ESCF with the intent of increasing awareness of ABPA among the participants in this study.

Pulmonary function and clinical observations in men with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) was once thought to be a distinct clinical entity, but genetic similarities in men with cystic fibrosis (CF) and CBAVD are described increasingly. We evaluated the clinical status, growth and nutritional state, and respiratory function of 18 men with CBAVD to determine whether these men with different CF transmembrane regulator (CFTR) genotypes may have clinical evidence of mild CF. Following a thorough history and examination, pulmonary function tests, sweat test, and renal ultrasound were performed. Genetic evaluation for 50 known CF mutations, screening for private mutations (single-strand conformational polymorphism and direct sequencing), and assay of the length of the polypyrimidine tract in the splice site acceptor of intron 8 was performed. A history of pulmonary disease was present in three, and an additional man had some features suggestive of malabsorption. Results of general physical examination and anthropomorphic measurements were unremarkable in all patients, with a mean (SD) body mass index of 26 (3). Pulmonary function tests of large and small airway function as well as lung volumes were normal in all except one whose results were consistent with moderate asthma. Five men were compound heterozygotes for CFTR mutations, four of whom had positive sweat tests (sweat chloride > 60 mEq/L). Twelve men were heterozygotes for CFTR mutations while no mutations were identified in one man. Although putative etiologic factors may suggest that men with CBAVD and CFTR mutations could be considered within the spectrum of clinical CF, the authors suggest that in men with CBAVD without any other clinical features of CF, the diagnosis of CF may not be made.

Transition from dynamically maintained to relaxed end-expiratory volume in human infants.

Newborn infants, in contrast to adults, dynamically maintain end-expiratory lung volume (EEV) above relaxation volume. The purpose of this study was to determine at what age children develop a breathing strategy that is relaxed, i.e., determined by the mechanical characteristics of the lung and chest wall. Forty studies were performed in 27 healthy infants and children aged 1 mo to 8 yr during natural sleep. Volume changes were recorded with the use of respiratory inductance plethysmography (RIP). The volume signal was differentiated to yield flow. Flow-volume representations were generated for a random sample of the recorded breaths to determine the predominant breathing strategy utilized, i.e., relaxed, interrupted, or indeterminate. The respiratory pattern was predominantly interrupted below 6 mo of age and predominantly relaxed over 1 yr of age. Mixed patterns were observed in children 6-12 mo of age. The number of breaths that could not be classified (indeterminate) decreased with age. Respiratory frequency measured from the sample of breaths decreased with age and was accompanied by an increase in expiratory time. We conclude that a relaxed EEV develops at the end of the first year of life and may be related to changes in the mechanical properties of the chest wall associated with growth as well as changes in respiratory timing.

Changes of time constants during infancy and early childhood.

We used respiratory inductance plethysmography to record tidal respiration in 27 healthy unsedated infants and children 1 mo to 8 yr of age during sleep. Rib cage and abdominal outputs were present at approximately equal gains and summed to obtain an estimate of volume. Flow-volume curves were generated from the uncalibrated volume signal and its flow derivative. Expiratory time constants (tau) were obtained by visually drawing a line through the linear portion of the expiratory flow-volume relationship. tau increased significantly during the first 10 mo of life. After 10 mo, the estimated rate of increase of tau for older children was less than 5% of the estimated initial rate and not significantly different from zero. Prolongation of tau was paralleled by an increase in expiratory time (Te), and no changes in Te/tau were observed in the first 2 yr of life. These changes in tau likely reflect the increase in lung compliance induced by rapid alveolar growth during infancy. After the first year, expiratory time constants appear to remain relatively constant and may be consistent with balanced changes in compliance and resistance beyond infancy.

Levalbuterol hydrochloride.

Racemic albuterol, a commonly used bronchodilator, is an exact 50:50 mixture of two enantiomers, R- and S-albuterol. Concern regarding increased mortality associated with the use of this beta-2 (beta 2) agonist triggered the study of both of these enantiomers separately. In vitro studies suggest that the two enantiomers have different binding affinities for beta-adrenoreceptors, may exert opposing effects on inflammation, demonstrate different effects on mucocilary transport, and display differing pharmacokinetics. Clinical studies comparing both enantiomers are few, of short duration, and often in small patient populations, and their results vary. R-albuterol has greater bronchodilatory effects than the racemate and may have anti-inflammatory properties. S-albuterol has markedly less affinity for the beta-adrenoreceptor. It was found to cause bronchoconstriction in animal models, but neither bronchoconstrictive nor pro-inflammatory effects have been conclusively demonstrated in human studies. The data available at present, while suggestive, are insufficient to conclusively recommend R-albuterol over the racemate. Further basic research and investigations in humans comparing both enantiomers at increasing doses over longer time periods are required to clarify the precise roles of R- and S-albuterol.

Thoracoabdominal asynchrony and ratio of time to peak tidal expiratory flow over total expiratory time in adolescents with cystic fibrosis.

Thoracoabdominal asynchrony (TAA) and the ratio of time to peak tidal expiratory flow over total expiratory time (TME/TE) have been used to assess airway obstruction in infants and adults. We obtained these measurements using calibrated respiratory inductance plethysmography (RIP) on 15 adolescents and young adults with cystic fibrosis (CF) and varying disease severity. The measurements were then compared to 15 normal age-matched controls. TAA was expressed as a phase angle (phi) calculated from the abdominal (AB) and ribcage (RC) signals acquired from scalar strip chart recordings. Using CODAS (DATAQ Instruments, Akron, OH) software, the analog signals were digitized, and the differentiated sum (AB + RC) signal was used to calculate TME/TE. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were obtained using RIP in all subjects. Subjects with CF had a significantly higher mean phi than the control subjects (15 degrees vs. 8 degrees, respectively, P = 0.01). In the CF patients the specificity of a high phi as an indicator of abnormality was 80%, while the sensitivity was 65%. There was no correlation in the magnitude of phi and disease severity as assessed by FVC or FEV1. There was no significant difference in TME/TE between the groups. We conclude that RIP-acquired phi, but not TME/TE, is a simple and useful method to detect the presence of airway obstructive disease. We speculate that the sensitivity of this method will increase in younger patients with more compliant chest walls and less air trapping. Longitudinal studies of phi in infants and young children with lung disease could help in assessing disease severity and progression in this population, in whom repeated measures are few and complex.

Reproductive health in males with cystic fibrosis: knowledge, attitudes, and experiences of patients and parents.

Males with cystic fibrosis (CF) are generally infertile as a result of aberrant development of Wolffian duct derivitives. The personal significance of this and related reproductive and sexual health (RSH) issues is unknown. We set out to describe the knowledge, attitudes, and experiences regarding RSH in a group of adolescent and adult males with CF, as well as the knowledge and attitudes of parents. This descriptive study was based on a semi-structured interview utilizing in-depth interview techniques. Questions included aspects of knowledge, attitudes, and experiences. Adolescent (aged 14-17 years) and adult (at least 18 years) males attending the Children's Hospital Cystic Fibrosis Clinic, Boston, MA, USA, or hospitalized at the Children's Hospital over that period were eligible; the accompanying parent of the adolescent was also interviewed. Consecutive eligible males were interviewed over a 3 month period. Summary data are presented, attitudinal data are analyzed qualitatively, and a selection of representative transcript data are reported to describe the range of opinions. Fifty males (10 adolescents, 40 adults) participated; this constituted a consecutive sample of 44% of the eligible clinic population. Ninety percent of adults, 60% of adolescents, and 50% of parents knew of male infertility. The mean age (+/-SD) at which adults recalled first hearing this was 16.0 +/- 4.7 years and 13.9 +/- 1.6 years for those adolescents who knew of infertility. Nineteen (48%) of adults and 5 (83%) of adolescents first heard about infertility from their health care providers. Ninety percent reported no major distress upon first hearing about infertility during adolescence. Increasing significance of infertility with maturity was reported by 12 men (30%); only 4 adults (10%) reported that infertility was not a significant aspect of CF. Forty percent knew that males with CF have a small volume ejaculate, but none had been told this by a health care provider. Thirty percent of men had semen analysis performed and all were azoospermic. We conclude that the majority of males with CF know of likely infertility. The significance of this knowledge changes with time. Poor knowledge and confusion surround a range of RSH issues in males with CF.

PIP: Reproductive and sexual health issues are often neglected in work with patients with chronic, life-limiting diseases. Aberrant development of Wolffian duct derivatives generally leads to infertility in men with cystic fibrosis. The reproductive health-related knowledge, attitudes, and experiences of adolescent and adult males with cystic fibrosis were investigated in a descriptive study conducted at the Children's Hospital Cystic Fibrosis Clinic in Boston, Massachusetts (US). Enrolled were 10 adolescents 14-17 years old (mean age, 16 years) and 40 adult men 18-53 years old (mean age, 29 years). 90% of adults, 60% of adolescents, and 50% of parents of adolescent patients were aware of the risk of infertility associated with cystic fibrosis. The average age at which the adult men first learned of this risk was 16 years. A health care provider was the source of this knowledge for 48% of adults and 83% of adolescents. 90% of adult men reported no major distress upon first hearing of the likelihood of infertility during adolescence; however, the emotional significance of possible infertility increased over time for 30%. 20% confused infertility with impotence. 30% of adult men had requested semen analyses and all were azoospermic. There was agreement among respondents that 14 years of age is an appropriate time for health care providers to initiate discussions about the impact of cystic fibrosis on reproductive health. Semen analysis is important to offer all men with cystic fibrosis, providing it is coupled with counseling if azoospermia is confirmed.

Respiratory diseases in the first year of life in children born to HIV-1-infected women.

Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.

Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

Reproductive and sexual health in males with cystic fibrosis: a case for health professional education and training.

PURPOSE: To survey the attitudes and clinical practice of health professionals to identify current practice and possible barriers to discussion of sexual and reproductive health issues in adolescent males with cystic fibrosis (CF). METHODS: An interview schedule was developed to seek information about attitudes to reproductive and sexual health in males with CF and to elicit details of reported professional practice of health care providers from four CF centers in Massachusetts. RESULTS: Of 32 health professionals interviewed, 66% informed parents about male infertility soon after diagnosis in infancy; 22% of those not informing parents at this time waited until later childhood or adolescence; and 12% reported they did not discuss these issues with parents during childhood or adolescence. All respondents reported they discuss infertility with male adolescents. The mean age thought most appropriate to discuss infertility was 13.8 (+/-2.2) years, although most do so at 15.2 (+/-2.8) years (p <.05). Fifty percent report routinely discussing that sexual performance is not affected by CF; 38% discuss the importance of condom use; 50% discuss normal sexual performance; 13% offer semen analysis to adolescents; and 3% inform males about small-volume ejaculates. Reproductive options are discussed with adolescents by 19% of clinicians. The themes of embarrassment, insufficient time, the difficulty of finding the "right" time, and insufficient training were identified as barriers to these discussions. CONCLUSIONS: Greater training for health professionals in the reproductive and sexual health issues of CF is a step to more complete, timely, and comfortable discussion of this area of health care.

Predictors of mucoid Pseudomonas colonization in cystic fibrosis patients.

RATIONALE: Chronic mucoid Pseudomonas aeruginosa within the airway in cystic fibrosis (CF) patients can determine prognosis. Understanding the risk factors of mucoid P. aeruginosa acquisition may change how we deliver care. This study aims to evaluate whether presence of risk factors reported to predict disease severity including gender, CFTR genotype, bacterial organisms in airway cultures, and serum levels of vitamins A and E, albumin, C-reactive protein, alpha 1-antitrypsin, and immunoglobulins increased the risk of mucoid P. aeruginosa acquisition. METHODS: Primary endpoint was age at first transition from negative to positive culture for mucoid P. aeruginosa. Cox proportional hazards regression with time-dependent covariates examined development of mucoid P. aeruginosa infection and its association with longitudinally measured serum biomarkers, pulmonary function, and culture results for other organisms. RESULTS: Median ages at CF diagnosis and at first culture were 0.55 and 5.7 years, respectively. Median number of cultures/patient was 17. Of the 323 subjects, 150 developed mucoid P. aeruginosa during a median 8.1 years' follow-up. In multivariate analysis, gender (relative hazard [RH] 0.55 for male vs. female, P = 0.001), number of DF508 alleles (RH 1.66 for 1 or 2 vs. 0, P = 0.04), FEV(1) % (RH 1.16 for 10% decrease, P = 0.008), and most recent Staphylococcus aureus status (RH 0.24 for positive vs. negative, P < 0.0001) remained statistically significant. CONCLUSION: Female gender, number of DF508 alleles, decreased lung function, and lack of S. aureus on recent sputum culture are important risk factors for early detection of mucoid P. aeruginosa.

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis.

INTRODUCTION: Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1beta, tumor necrosis factor alpha, and interleukin-6. METHODS: We studied 32 outpatients (18 females; mean age: 26.2+/-7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1beta and BMD at all sites. RESULTS: In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. CONCLUSIONS: These findings may have therapeutic implications for enhancing bone density in these patients.

Effects of theophylline on urinary excretion of cyclic AMP, calcium, and phosphorus in normal subjects.

The present study was designed to examine the effects of acute theophylline administration on urinary excretion of cyclic adenosine monophosphate (cAMP), calcium, and phosphorus in normal subjects. The results demonstrated that at therapeutic doses (5 mg i.v./kg body weight) theophylline exerted a distinct biologic effect on renal tubular activity in 5 normal subjects: an increase in nephrogenous cAMP accompanied by a rise in phosphate and calcium urinary excretion. Beyond the clinical implications, the data suggest that theophylline, in contrast to parathyroid hormone, may be acting via cAMP to exert both its phosphaturic and calciuric effect on renal tubules.