Differential diagnosis in pediatric radiology, 2nd ed. By Leonard E. Swischuk and Susan D. John. Baltimore: Williams & Wilkins, 1995, 482 pp

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38602/1/1950210305_ftp.pd

Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations

<p>Abstract</p> <p>Background</p> <p>Cystic Fibrosis (CF) is a life-shortening genetic disease in which ~80% of deaths result from loss of lung function linked to inflammation due to chronic bacterial infection (principally <it>Pseudomonas aeruginosa</it>). Pulmonary exacerbations (intermittent episodes during which symptoms of lung infection increase and lung function decreases) can cause substantial resource utilization, morbidity, and irreversible loss of lung function. Intravenous antibiotic treatment to reduce exacerbation symptoms is standard management practice. However, no prospective studies have identified an optimal antibiotic treatment duration and this lack of objective data has been identified as an area of concern and interest.</p> <p>Methods</p> <p>We have retrospectively analyzed pulmonary function response data (as forced expiratory volume in one second; FEV₁) from a previous blinded controlled CF exacerbation management study of intravenous ceftazidime/tobramycin and meropenem/tobramycin in which spirometry was conducted daily to assess the time course of pulmonary function response.</p> <p>Results</p> <p>Ninety-five patients in the study received antibiotics for at least 4 days and were included in our analyses. Patients received antibiotics for an average of 12.6 days (median = 13, SD = 3.2 days), with a range of 4 to 27 days. No significant differences were observed in mean or median treatment durations as functions of either treatment group or baseline lung disease stage. Average time from initiation of antibiotic treatment to highest observed FEV₁was 8.7 days (median = 10, SD = 4.0 days), with a range of zero to 19 days. Patients were treated an average of 3.9 days beyond the day of peak FEV₁(median = 3, SD = 3.8 days), with 89 patients (93.7%) experiencing their peak FEV₁improvement within 13 days. There were no differences in mean or median times to peak FEV₁as a function of treatment group, although the magnitude of FEV₁improvement differed between groups.</p> <p>Conclusions</p> <p>Our results suggest that antibiotic response to exacerbation as assessed by pulmonary function is essentially complete within 2 weeks of treatment initiation and relatively independent of the magnitude of pulmonary function response observed.</p

Adherence with tobramycin inhaled solution and health care utilization

<p>Abstract</p> <p>Background</p> <p>Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization.</p> <p>Methods</p> <p>We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories.</p> <p>Results</p> <p>Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768).</p> <p>Conclusions</p> <p>Use of TIS did not reflect recommended guidelines and may impact other health care utilization.</p

Identifying barriers to treatment adherence and related attitudinal patterns in adolescents with cystic fibrosis

Introduction The treatment of cystic fibrosis (CF) is directed toward correction of organ dysfunction and relief of symptoms resulting from the disease. Lack of adherence to daily treatment regimens may have substantial short-term and long-term effects on patients with CF. In this study, we attempted to identify barriers to treatment adherence which could be predicted by objective measures and explore ways to improve adherence in adolescents with CF. Methods A questionnaire was given to patients 12.0–20.9 years of age, designed with focus on specific barriers to adhering to treatment plan and related attitudinal patterns. Observational and analytical results were collected. Results We obtained questionnaires and objective health data for 60 respondents. The most commonly identified barriers to adherence were forgetting or losing medications (32/60) and being too busy (23/60). Attitudinal patterns that played a significant role for nonadherence included unintentional forgetting (40/60), feeling that following CF treatments resulted in less freedom in their lives (30/60), and believing it is acceptable to miss a treatment every few days (18/60) or to miss treatments when busy (18/60). Discussion There were a few statistically significant differences of adherence patterns between demographic subgroups in our study. Males were more likely to agree that it is acceptable to miss doses if they are made up with extra doses later (24% vs. 3%, P  = 0.04). Patients who perceived themselves to be less healthy agreed more to statements of limited freedom, nonsympathetic medical providers, and difficulty adhering during times of decreased symptoms. This highlights an unexpected risk: as CF progresses and patients perceive themselves to be less healthy, they may become less likely to be adherent during the periods they are feeling the best, while at the same time becoming less likely to perceive empathy from their physicians. Conclusions Survey results describe a variety of beliefs and attitudinal patterns which contribute to nonadherence in CF treatment, especially relating to time management. While patients largely understood the importance of treatments to their health, predictors of risky behaviors could lead to targeted interventions by CF centers to address these challenges and improve adherence. Pediatr Pulmonol. 2010; 45:450–458. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71362/1/21195_ftp.pd

The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease

Objectives To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). Methods Thirty-two CF patients with mostly mild lung disease age ≥6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5 ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. Results Using two tailed paired t -test, the percent maximum HRCT score decreased by 1.4 ± 2.6% (mean ± SD) ( P  = 0.049) and 0.3 ± 2.8% ( P  = 0.63) for the TSI group and decreased by 0.1 ± 1.5% ( P  = 0.74) and increased by 0.6 ± 1.8% ( P  = 0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was −0.24/day ( P  = 0.02) and −0.03/day ( P  = 0.22), and for the control group the change was −0.01 ( P  = 0.93) and 0.02 ( P  = 0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF 25–75 % and FEV 1 % changes were not statistically significant using both analyses. Conclusion HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI. Pediatr Pulmonol. 2010; 45:440–449. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71358/1/21188_ftp.pd

Liquid ventilation in an infant with pulmonary alveolar proteinosis

Partial liquid ventilation (PLV) has been applied in various pulmonary diseases. We describe the use of partial liquid ventilation as a lavage method following normal saline (NS) lavage in an infant with pulmonary alveolar proteinosis (PAP) and severe hypoxemia. A 6 weeks old 3.4 kg former 36 weeks gestation boy on supplemental oxygen was transferred to our NICU with persistent tachypnea, dry cough, and increasing oxygen requirements. A lingular open lung biopsy revealed PAP. He developed progressive respiratory failure requiring ventilatory support, necessitating conventional NS lavage, followed by lung lavage with perflubron (LiquiVent; Alliance Pharmaceutical Corp. and Hoechst Marion Roussel) while on venovenous extracorporeal life support (ECLS). Lung lavage with NS and perflubron yielded minimal cloudy effluent. Gas exchange and pulmonary function deteriorated following NS lavage and attempts to discontinue ECLS were poorly tolerated. In contrast, tidal volume, P a O 2 , and pulmonary compliance increased after PLV, while the (A-a) DO 2 decreased to a point where ECLS was no longer required. Once perflubron was added repeatedly to the ventilator circuit to correct for evaporation over the 4 days of PLV. Cardiovascular status remained stable for several days; however, eventually he required reinitiation of ECLS and more mechanical ventilatory support with each trial off ECLS. He was maintained on high pressures and F i O 2 without any possibility to wean him from mechanical ventilation. Life support was withdrawn 1 month after admission. The survival from PAP in infants remains dismal, even with total lung NS lavage. While both NS and perflubron lavage in this patient were not effective in removing the proteinaceous alveolar debris, PLV following NS lavage was associated with an improvement in gas exchange and lung compliance. Pediatr Pulmonol. 1998; 26:283–286. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38603/1/8_ftp.pd

An adult cystic fibrosis patient presenting with persistent dyspnea: case report

BACKGROUND: Persistent dyspnea is a common finding in the cystic fibrosis patient that typically leads to further work up of an alternative pulmonary etiology. Adult cystic fibrosis patients; however, are growing in numbers and they are living into the ages in which coronary artery disease becomes prevalent. Coronary disease should be included in the consideration of diagnostic possibilities. CASE PRESENTATION: A 52-year-old white male with cystic fibrosis was evaluated for exertional dyspnea associated with vague chest discomfort. Diagnostic testing revealed normal white blood cell, hemoglobin and platelet count, basic metabolic panel, fasting lipid profile, HbA1c, with chest radiograph confirming chronic cystic findings unchanged from prior radiographs and an electrocardiogram that revealed sinus rhythm with left anterior fascicular block. Stress thallium testing demonstrated a reversible anteroseptal perfusion defect with a 55% left ventricular ejection fraction. Heart catheterization found a 99% occlusion of the left anterior descending artery extending into the two diagonal branches, with 100% obstruction of the left anterior descending artery at the trifurcation and 70% lesion affecting the first posterior lateral branch of the circumflex artery. CONCLUSION: This case report represents the first description in the medical literature of a cystic fibrosis patient diagnosed with symptomatic coronary artery disease. Applying a standard clinical practice guide proved useful toward evaluating a differential diagnosis for a cystic fibrosis patient presenting with dyspnea and chest discomfort

Phenotypic heterogeneity in cystic fibrosis

We have confirmed heterogenity in CF using a different combination of primary clinical variables than those used in previous studies. Subgroupings of individuals with similar levels of sweat chloride were independent of the clustering based on level of pancreatic enzyme supplementation and degree of pulmonary involvement. Data from families with multiple CF children are consistent with the hypothesis that the genetic etiology of CF involves two or more genes that modify the expression of the primary gene defect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38234/1/1320130209_ftp.pd

The L441P Mutation of Cystic Fibrosis Transmembrane conductance Regulator and its Molecular Pathogenic Mechanisms in a Korean Patient with Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder usually found in populations of white Caucasian descent. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl was admitted complaining of coughing and greenish sputum. Chest radiographs and computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The patient had chronic diarrhea and poor weight gain, and the abdominal pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis test. The chloride concentration of sweat samples taken from both forearms of the pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a comprehensive search for mutations in the CFTR gene, the patient was found to carry the non-synonymous L441P mutation in one allele. Molecular physiologic analysis of the L441P mutation of CFTR revealed that the L441P mutation completely abolished the CFTR Cl- channel activity by disrupting proper protein folding and membrane trafficking of CFTR protein. These results confirmed the pathogenicity of the L441P mutation of CFTR circulating in the Korean population. The possibility of CF should be suspected in patients with chronic bronchiectasis, although the frequency of CF is relatively rare in East Asia