Clinical efficacy of CFTR modulator therapy in people with cystic fibrosis carrying the I1234V mutation.

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) mutation I1234V (I1234V, p.Ile1234Val, c.3700A>G), is a missense-mutation that creates a cryptic splice site, with the formation of a protein lacking 6 amino acids, that is misfolded and misprocessed.

The new face of cystic fibrosis in the era of population genetic carrier screening.

Background: Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features.

Methods: This was a retrospective national study.

Congenital Central Hypoventilation Syndrome in Israel-Novel Findings from a New National Center.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal-dominant disorder of the autonomic nervous system that results from mutations in the gene. A national CCHS center was founded in Israel in 2018. Unique new findings were observed.

Antimicrobial Peptides against Multidrug-Resistant Biofilm from Cystic Fibrosis Patients.

Lung infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by . Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like . Antimicrobial peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity.

Spontaneous pneumothorax-When do we need to intervene?

Background: Pneumothorax can be classified as traumatic, iatrogenic or spontaneous (SP), which can be subdivided into primary spontaneous pneumothorax (PSP), a condition without preexisting lung disease, or secondary spontaneous pneumothorax (SSP) a complication of a preexisting lung disease. Recurrence rate of PSP is 30% whereas for SSP rate is unknown. This article explores the experience of a tertiary center over 20 years.

Advanced Lung Disease in Patients with Cystic Fibrosis Is Associated with Low Diffusion capacity.

Background: The single-breath diffusing capacity of the lungs (DLCOSB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VASB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCOSB) is the DLCOSB divided by VASB.

Author Correction: Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Phenotypic and molecular characteristics of CF patients carrying the I1234V mutation.

Background: The Mutation I1234V is a CF causing mutation; however the mechanisms leading to loss of function are not fully understood. In this study, we aimed to characterize phenotypically individuals with the I1234V variant, and to gain a structural point of view of the mutant CFTR using computational studies.

Methods: We conducted a retrospective descriptive study, reviewing the clinical records of 9 Israeli patients.

The benefits of mechanical insufflator-exsufflator compared to autogenic drainage in adults with cystic fibrosis.

Background: Autogenic drainage (AD) is used for airway clearance in individuals with cystic fibrosis (CF). The mechanical insufflator-exsufflator (MI-E) device is commonly used in patients with neuromuscular diseases for airway clearance by increasing inspiratory volume and expiratory flow. MI-E use has not been studied extensively in CF patients.

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study.

Correction to: Ambulatory blood pressure profiles in familial dysautonomia.

Unfortunately, the original version of this article contained.

Pilot study to test inhaled nitric oxide in cystic fibrosis patients with refractory Mycobacterium abscessus lung infection.

Background: Airways of Cystic Fibrosis (CF) patients are Nitric Oxide (NO) deficient which may contribute to impaired lung function and infection clearance. Mycobacterium abscessus (M. abscessus) infection prevalence is increasing in CF patients and is associated with increased morbidity and mortality.

Resting Energy Expenditure in Patients With Familial Dysautonomia: A Preliminary Study.

Objectives: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy characterized by chronic lung disease and cyclic vomiting due to hyper-adrenergic crises. Most FD patients are in a depleted nutritional state; however, the phenotype of the disease is quite different between patients, as for the severity of lung disease and the intensity and frequency of these pathognomonic crises. In this study we wanted to investigate whether resting energy expenditure (REE) levels are increased in this population, and if correlations exist between REE levels and phenotype severity.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

Background: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia.

Omalizumab in allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by a Th2 response, serum eosinophilia, and increased total serum IgE to . ABPA occurs in cystic fibrosis (CF) and asthma. Omalizumab is a humanized recombinant monoclonal antibody against IgE.

Ambulatory blood pressure profiles in familial dysautonomia.

Objective: Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability.

A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia.

Background: Chronic lung disease is a leading cause of premature death in patients with familial dysautonomia (FD). A significant number of patients have obstructive airway disease, yet it is not known whether this is pharmacologically reversible.

Methods: We conducted a double-blind, placebo-controlled, randomized clinical trial comparing the beta 2 agonist albuterol with the muscarinic blocker ipratropium bromide in patients homozygous for the IKBKAP founder mutation.

Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience.

Background: Ivacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse.

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.

Background: Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations.

Consequences of Expiratory Flow Limitation at Rest in Subjects with Cystic Fibrosis.

Rationale: Expiratory flow limitation at resting tidal volume (EFLTV) presents a severe mechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis.

Objectives: To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis.

Methods: Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12 ± 3.

Impact of an extended challenge on the effectiveness of β-lactam hypersensitivity investigation.

Background: Drug provocation tests (DPTs) are the gold standard in the diagnosis of β-lactam hypersensitivity. However, no consensus exists on the need for extended provocation tests, even though the effectiveness of the short DPT is relatively low and there has been an increase in the relative incidence of nonimmediate hypersensitivity reactions.

Objective: To evaluate the effectiveness of a 7-day (extended) DPT compared with a 1-day-only (short) DPT in the management of hypersensitivity reactions to β-lactam antibiotics.

Tracheal diverticula in cystic fibrosis-A potentially important underreported finding on chest CT.

Background: We aim to assess the prevalence and describe characteristics of tracheal diverticula (TD) in patients with cystic fibrosis (CF).

Methods: This retrospective study included 92 patients with known CF treated in our medical center who had available chest CT, performed between 2001 and 2013. Presence, number, size, and location of TD were recorded on the most recent chest CT.

TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability.

Background: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).

Glucose intolerance in cystic fibrosis as a determinant of pulmonary function and clinical status.

Background: Cystic fibrosis related diabetes (CFRD) is associated with a decrease in pulmonary function and nutritional status. We investigated the clinical significance of impaired glucose tolerance (IGT) in cystic fibrosis (CF) patients.

Methods: Fifty-five CF patients (aged 22.