Michal Gur

Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis

Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. OBJECTIVES To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. METHODS In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. RESULTS Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. CONCLUSIONS Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure.

The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening

BACKGROUND Population carrier screening (PCS) has been available in Israel since 1999 and universally subsidized since 2008. We sought to evaluate its impact. METHODS A retrospective review of governmental databanks, the national CF registry and CF centers. RESULTS CF rate per 100,000 live births has decreased from 14.5 in 1990 to 6 in 2011. From 2004-2011 there were 95 CF births: 22 utilized PCS; 68 (72%) had 2 known CFTR mutations; 37% were pancreatic sufficient. At diagnosis, age was 6 (0-98) months; 53/95 had respiratory symptoms, 41/95 failure to thrive and 19/95 pseudomonas. Thirty-four (36%) were Arabs and 19 (20%) orthodox Jews, compared to 20% and 8% respectively, in the general population. CONCLUSIONS PCS markedly reduced CF birth rates with a shift towards milder mutations, but was often avoided for cultural reasons. As children regularly have significant disease at diagnosis, we suggest a balanced approach, utilizing both PCS and newborn screening.

The use of telehealth (text messaging and video communications) in patients with cystic fibrosis: A pilot study

Background Poor communications between cystic fibrosis (CF) patients and health-care providers may result in gaps in knowledge and misconceptions about medication usage, and can lead to poor adherence. We aimed to assess the feasibility of using WhatsApp and Skype to improve communications. Methods This single-centre pilot study included CF patients who were older than eight years of age assigned to two groups: one without intervention (control group), and one with intervention. Each patient from the intervention group received Skype-based online video chats and WhatsApp messages from members of the multidisciplinary CF team. CF questionnaires, revised (CFQ-R) scores, knowledge and adherence based on CF My Way and patients satisfaction were evaluated before and after three months. Feasibility was assessed by session attendance, acceptability and satisfaction survey. Descriptive analysis and paired and non-paired t-tests were used as applicable. Results Eighteen patients were recruited to this feasibility study (nine in each group). Each intervention group participant had between four and six Skype video chats and received 22–45 WhatsApp messages. In this small study, CFQ-R scores, knowledge, adherence and patient satisfaction were similar in both groups before and after the three-month intervention. Conclusions A telehealth-based approach, using Skype video chats and WhatsApp messages, was feasible and acceptable in this pilot study. A larger and longer multi-centre study is warranted to examine the efficacy of these interventions to improve knowledge, adherence and communication.

Pulmonary manifestations of prolidase deficiency

Prolidase deficiency is a rare autosomal recessive disease, in which pulmonary manifestations have been sporadically reported.

Cardiopulmonary exercise test to quantify enzyme replacement response in pediatric Pompe disease

Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric Pompe patients.

Early prenatal ultrasound diagnosis of congenital thoracic malformations

Abstract Objectives: To evaluate and describe the spectrum and rate of congenital thoracic malformations (CTMs) diagnosed by early prenatal sonography (gestational age (GA) less than 16 weeks). Methods: A retrospective, cross-sectional analysis of prenatal ultrasound screening tests in a community-based clinic. Results: In 2001–2017, 31 261 prenatal ultrasound tests detected 31 CTMs at a gestational age of 15.2 (range, 11.6–16.0) weeks. The most common malformation was congenital pleural effusion (CPE) (15 fetuses, 0.48/1000), followed by congenital diaphragmatic hernia (CDH) (10 fetuses, 0.32/1000). Pulmonary hypoplasia (PH), congenital pulmonary airway malformation and broncho-pulmonary sequestration appeared in much smaller proportions (three, two and one fetuses, respectively). Most CTMs were associated with additional fetal lesions (15 fetuses, 48%). All early CDH (10 fetuses) and PH (three fetuses) and 6/15 with CPE had termination of pregnancy or missed abortions. Conclusions: Prenatal ultrasound before 16 GA was able to detect CTMs in 0.99/1000 of screening ultrasound (US) performed. Most CTMs tended to appear with multiple lesions and were associated with unfavorable outcomes. Earlier prenatal diagnosis may enable early termination of pregnancy in fetuses with lethal malformations.

The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews

BACKGROUND The Q359K/T360K mutation, described in Jewish CF patients of Georgian decent, is of questionable clinical significance. METHODS Clinical records of patients with the Q359K/T360K mutation from three CF centers were studied for phenotypic expression and putative mechanism of dysfunction. Computer models of mutant CFTR were constructed. RESULTS Nine patients (4 homozygous) of Georgian Jewish origin were included. Age at diagnosis was 9.4 (0.25-38.2) years, median (range). Sweat chloride was 106 ± 13 meq/L, mean ± SD. Nasal Potential Difference performed in three, was abnormal. All had pulmonary symptoms since early childhood and bronchiectasis. Median FEV1 was 88 (40-121)%. Five had chronic mucoid P. aeruginosa. Homozygous patients were pancreatic insufficient. Enzyme supplementation was initiated at 3.8 (1-14.7) years, median (range). Structural models hint at possible interference of this mutation with transmembrane chloride transport. CONCLUSION In our cohort, the Q359K/T360K mutation resulted in a severe CF phenotype, although with residual early CFTR function. The CFTR2 database should consider defining this mutation as CF-causing.

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa

INTRODUCTION CF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy. PURPOSE Our aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods. MATERIALS AND METHODS A prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle). RESULTS Nineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase]. CONCLUSIONS The results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

Chest computed tomography scores in patients with cystic fibrosis colonized with methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin‐resistant Staphylococcus aureus (MRSA) is an important pathogen in cystic fibrosis (CF), with increasing incidence in recent years. We examined the association between bacterial colonization in the sputum (MRSA with or without pseudomonas (PA)) and computed tomography (CT) scores in CF patients.

Halotherapy as asthma treatment in children: A randomized, controlled, prospective pilot study

Asthma is a chronic inflammatory disorder requiring intermittent or continuous anti‐inflammatory therapy. Patients often turn to alternative treatments as complements or replacements to conventional treatments. We aimed to evaluate the effect of salt room chambers (halotherapy) on bronchial hyper‐responsiveness (BHR), fractional exhaled nitric oxide (FeNO), and quality of life in children with asthma.