Low gammaglobulin subclass 2 levels in paediatric cystic fibrosis patients followed over a 2-year period

The aim of this study was to relate serum immunoglobulin G2 subclass levels in a large paediatric population with cystic fibrosis, to clinical status and antibody levels to Haemophilus influenzae type b and Streptococcus pneumoniae and to observe any changes over a 2-year period. IgG subclasses were measured in 131 patients. Results were compared with levels from age-related normal population data. The following clinical data were collected at baseline and 2 years later; genotype: height, weight, and BMI z-scores: FEV1 (as percent predicted): Shwachman-Kulczcyki and Northern chest X-ray scores: Pseudomonas aeruginosa status. Antibody levels to H. influenzae type b and S. pneumoniae measured at baseline were related to IgG2 level. There was a reduction in the prevalence of low levels of IgG2 from 29% to 10% over the 2-year period. Low levels of IgG2 were not associated with any decline in clinical well-being. Low levels of IgG2 alone were associated with low antibody levels to S. pneumoniae. Low levels of IgG2 and low levels of antibody to H. influenzae and S. pneumoniae were not associated with any decline in clinical well-being. Children with high levels of IgG2 had worse lung function, worse Shwachman-Kulczcyki and Northern chest X-ray scores and higher levels of P. aeruginosa infection. Children with low IgG2 levels were not worse clinically compared to those with normal or high IgG2 levels. High IgG2 levels were associated with a worse clinical status.     

Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed for 12 months at regular clinic visits. Routine sputum/laryngeal aspirations were tested with PCR for 7 respiratory viruses. Antibodies against C. pneumoniae, M. pneumoniae and B. pertussis were measured every 3-4 months. FEV-1, FEF(25-75) and specific airway resistance, "viral" symptoms and bacterial culture were recorded. RESULTS: Ninety-seven viral and 21 atypical bacterial infections were found. FEV-1 was significantly reduced during viral infection (-12.5%, p=0.048), with the exception of rhinovirus infection. A small change in FEV-1 (-3%) was seen during atypical bacterial infection (p=0.039). Viral and atypical bacterial infections caused no change in type and frequency of bacterial culture. Positive predictive value of "viral symptoms" was low (0.64%). Eight patients received "unnecessary" antibiotics because of viral symptoms. CONCLUSIONS: Some viral infections and atypical bacterial infections affect FEV-1 acutely. Viral infections did not precipitate bacterial infection or change of colonisation. Clinical symptoms failed to diagnose viral infection accurately. Routine surveillance for virus or atypical bacteria seems not to be justified in this patient category.     

Anaerobic exercise in pediatric cystic fibrosis

Anaerobic fitness is important for daily functioning of children with cystic fibrosis (CF). The aim of this study was to assess the determinants of anaerobic performance in CF. Anaerobic performance was measured in 39 children with CF (mean age, 13.2 +/- 1.8 (SD) years, forced expired volume in 1 sec (FEV(1)) 81.6 +/- 22.1% predicted), using a Wingate anaerobic test. Significant associations were found for peak power (PP) and mean power (MP) with fat-free mass (FFM) body weight, body mass index, maximal isometric muscle force, and aerobic capacity. Pulmonary function was correlated with anaerobic indices when controlled for FFM. Multiple regression analysis indicated that FFM and FEV(1) accounted for 82% and 86% of the variability in PP and MP, respectively. Patients with moderate CF (FEV(1) < 80%), as compared to mild CF (FEV(1) >/= 80%), had higher PP (difference = 85 W, 95% CI = 27-144 W) and MP (difference = 53 W, 95% CI = 42-63 W) at equivalent FFM. Our results indicate that FFM and pulmonary function are important determinants of anaerobic exercise performance in children with CF. With progression of pulmonary disease, anaerobic performance may be enhanced.     

The “worth” of routine spirometry in a cystic fibrosis clinic

In our cystic fibrosis clinic, all patients older than 6 years perform spirometry at each visit just before being seen by the health care team. Upon review, we determined that our perceived rationale for this practice was that the medical history fails to detect deterioration in a sizable minority of patients whose pulmonary decline can be detected by spirometry. Furthermore, the literature and our own experience indicates that physical examination frequently will not detect changes in pulmonary status until the changes are advanced. As part of an ongoing quality/cost assessment, we decided to challenge our rationale for performing routine spirometry. Using standard methodology, we developed a six-item Likert style questionnaire, the purpose of which was to assess perceived changes in pulmonary symptoms since the last clinic visit. The questionnaire had an acceptable degree of internal consistency (Cronbach's alpha = 0.92), although the question about sputum production showed the least correlation with responses to other items. We administered the questionnaire to 103 consecutive different patients and examined the association between reported changes in symptoms and actual changes in spirometric outcomes. Overall, there was a statistically significant, but clinically weak association between symptom scores and change in FEV₁, r² = 0.16, P < 0.001. Twenty-three patients had a decline in FEV₁ of ⩾10% from one clinic visit to the next. Depending on the method used to place symptom scores into categories indicating that pulmonary symptoms were “worse,” “same,” or “better” than at the last clinic visit, 40–60% of these 23 patients indicated they felt the “same” or “better.” We conclude that spirometry is a justifiable part of all clinic visits for patients with cystic fibrosis, assuming that one would want to detect and treat declines in pulmonary status before they become advanced. Pediatr Pulmonol. 1998; 25:231–237. © 1998 Wiley-Liss, Inc.     

Multiresistant Pseudomonas aeruginosa in a pediatric cystic fibrosis center: natural history and implications for segregation

It has been suggested that cystic fibrosis (CF) patients harboring multiresistant (MR) Pseudomonas aeruginosa (PA) should be seen in separate clinics. The aim of this study was to test the feasibility of this by longitudinally studying the consistency of isolates of MRPA in individuals. We analyzed all respiratory tract cultures undertaken in 1 year from a pediatric CF clinic population (n = 367). PA was classified as MR according to the definition of the American CF Foundation: resistance to all agents in at least two of the following groups of antibiotics: beta-lactams, aminoglycosides, and fluroquinolones. PA was cultured from 96 children during the year of study. Thirty-six were infected with at least one MR strain. Following initial identification of MRPA, MR in subsequent cultures was highly variable. Twenty-three of 36 patients had subsequent cultures in which PA was identified. However, 21 of 23 patients had at least one isolate that was not MR following detection of MRPA. The variability with time in isolation of MR strains from individuals demonstrates the potential difficulties in designing segregation policies based on antibiotic sensitivity patterns.     

Evaluation of a cystic fibrosis transition program from pediatric to adult care

Purpose

As the cystic fibrosis (CF) patient population median survival increase, the need for transitioning their care to adult care centers increase as well. We have a structured transition program since the early 1980s. The purpose of this study is to evaluate the experiences and opinions of patients in our adult CF center who went through a formal transition versus those who did not, in an attempt to evaluate the overall process and to identify means for improvement.

Methods

A questionnaire was given to adult CF patients at the University of Michigan during a clinic visit or inpatient hospitalization, after consent was obtained. Inclusion criteria included diagnosis of CF in childhood, previous care in a pediatric center, and current participation in our adult CF clinic.

Results

A total of 91 patients completed the questionnaire. 44 went through our structured transition program. On average, patients who participated in a formal transition process had higher satisfaction with both CF programs, perceived health status, and independence but no differences in their level of anxiety about transferring to the adult program. Patient opinions regarding when to transfer care were considered more often in patients who participated in a transition program (88% vs. 62% and P = 0.02).

Conclusion

Although structured transitions programs do not appear to decrease patient anxiety during this stressful period, it does appear to improve patient satisfaction, perceived health status, and independence. These findings suggest that establishing a transition program could be important in optimizing patient health, continuity of care and improving adherence. Pediatr Pulmonol. 2013; 48:658–665. © 2012 Wiley Periodicals, Inc.     

Effect of Burkholderia cepacia infection in the clinical course of patients with cystic fibrosis: a pilot study in a Sydney clinic

BACKGROUND: Colonisation with Burkholderia cepacia complex in patients with cystic fibrosis (CF) has been associated with adverse outcomes. The aim of the present study was to determine the actuarial survival of CF patients colonized with B. cepacia and to evaluate the efficacy of the Royal Prince Alfred Hospital segregation policy. A secondary aim was to characterize the specific genomovars and strains of B. cepacia isolated in an Australian clinic. METHODS: Retrospective review of spirometric and microbiological data on all patients colonized with B. cepacia. Each B. cepacia-colonized subject was matched with three case-control subjects. Phenotype and genomovar typing, random amplified polymorphic DNA strain type and B. cepacia epidemic strain marker analyses were performed. The effect of B. cepacia colonization on transplant-free survival was estimated by Cox's proportional hazards regression using the entire clinic population. RESULTS: Fifteen patients were colonized with B. cepacia, of whom six (40%) had died from CF-related disease by August 1998, compared with 30 of 173 (17.3%) of the entire clinic population. Cepacia status had a significant adverse effect on survival, with a hazard ratio of 2.16 (95% confidence interval 1.0-4.69; P = 0.05). The outcome was variable in subgroups of B. cepacia. DISCUSSION: Colonization with B. cepacia had a significant adverse effect on survival within the study population. Genomovar and strain typing contributed usefully in accessing the effectiveness of the hospital's segregation policy in preventing cross-colonization.     

Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis

Presentation

Patient is a 6‐year‐old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF.

Course

I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement.

Discussion

This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.

     

Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years). Four of the 6 had also received courses of intravenous colistin in the year before the first isolation of CRPA. No impact of CRPA acquisition on respiratory function, clinical condition, or radiological parameters could be demonstrated. Four of the 6 children carried isolates of CRPA indistinguishable on genotyping. Two of these 4 children were sisters. The other 2 were on the same ward together at time of first isolation, and subsequently shared overlapping admissions with one of the sisters.While there is no conclusive evidence for the route of transmission, the frequency of overlapping in-patient admissions between 3 of these patients is suggestive of patient-to-patient transfer in the nosocomial setting.CF clinicians should be aware that colistin resistance can occur in P. aeruginosa, and some of these strains are capable of spread within CF units.