We teamed together our pediatric pulmonology, cardiology and gastroenterology departments to screen for Hepatopulmonary Syndrome (HPS). HPS is a liver-induced lung disorder resulting from a combination of liver disease, pulmonary vascular dilatation, and a defect in oxygenation. It can complicate any chronic liver disease, but is most commonly associated with portal hypertension.
2% to 8% of patients with cystic fibrosis (CF) suffer from severe liver disease with portal hypertension, but we only knew of one patient with CF who had been diagnosed with HPS. We suspected that HPS is underdiagnosed in the CF population because of their pre-existing respiratory disease. We decided to screen our patients who might be at risk, and actually found someone who did have an undiagnosed case of HPS. We advocate for routine screening for every patient with CF who also has liver disease and portal hypertension. Our findings were published in Chest's February 2016 edition.
Volume 149, Issue 2, February 2016, Pages e35–e38
For the full article:
Treatment of Cystic Fibrosis in Low-income Countries
Enshrined in the constitution of the WHO is a basic human right to have access to the “highest attainable standard of health” irrespective of socioeconomic status. The current cystic fibrosis care guidelines are generally designed to be used in developed countries; and result in patients with CF enjoying better quality of life and living longer than ever before. In contrast, the guidelines include treatments not available in low-income regions; and patients with CF living in these regions tend to be diagnosed later, be more malnourished, and have worse lung functions.
We feel countries with adequate health-care resources are not absolved from assisting countries whose access to cystic fibrosis care is restricted by economic or other challenges. Treatment strategies for cystic fibrosis can be adapted to improve the longevity and quality of life for these disadvantaged patients. Our experience in cooperative arrangements, especially in Gaza and the West Bank, has shown that enhancement of the care of children with CF, even in conflict-led, resource-poor regions, is possible through the implementation of these adjustments:
Educating the medical community and the general public to increase awareness to help get an earlier diagnosis.
A CF care center, albeit minimally staffed
Drinking enough fluids with adequate salt supplementation is crucial, , especially in warm climates.
Pancreatic enzymes, a high calorie, high fat diet and fat-soluble vitamins are essential. This means 120–160% of the normal recommended daily calorie allowance, with 35–40% of the calories coming from fat. Such a diet is relatively affordable, when based on local products, . If fat-soluble preparations of vitamins A, D, and E are not available, foods rich in these vitamins can be consumed.
Offer empathetic and culturally appropriate care to overcome economic, educational, and cultural barriers, and gain adherence to the required therapies. This is difficult enough in the most ideal of circumstances, but they can be overcome.
Airway clearance is the keystone for lung clearance. This involves:
Manual Chest Physiotherapy (CPT) should be started even in patients who are asymptomatic.
Hypertonic saline is inexpensive and easily prepared (by adding 7 g of sodium chloride granules to 100 mL of boiled water) and can be used as a first line inhalation treatment.
Devices for mechanical airway clearance specifically developed for cystic fibrosis— including oscillating positive expiratory pressure (PEP) devices—can be purchased relatively inexpensively and shipped to the patients’ homes.
Malena Cohen-Cymberknoh, David Shoseyov, Oded Breuer, Mahmoud Shamali, Michael Wilschanski, Eitan Kerem
ADHD in Patients with Cystic Fibrosis
We found that the occurrence of ADHD in patients with CF is higher than expected in the general population. The specific characteristics of this connection might also be related to chronic inflammatory processes.
The daily treatments required to control CF demand time, energy, and persistence. Attention deficit hyperactivity disorder (ADHD), found in about 7% of the general population, may be another possible barrier to adherence. ADHD is associated with functional impairment in multiple settings including self-care. Increased inflammatory marker levels in ADHD-patients suggest a probable association with chronic inflammatory illnesses. It is believed that patients who suffer from ADHD “on top” of chronic diseases, may experience greater difficulty in controlling their primary disease. Few studies have analyzed the influence of ADHD in CF patients.
We aimed to determine the rate and characteristics of ADHD in patients with CF. 122 patients older than 6 years of age were recruited from the Hadassah, Schneider and Rambam CF centers. Patients and parents completed the DSM-5 ADHD questionnaire and patients performed the online d-CPT MOXO analysis.
45% of our group showed characteristics that may be compatible with ADHD. 16% matched all DSM's criteria, whereas 29% fulfilled only part of the criteria with pathologic results seen in the MOXO analysis requiring further evaluation by a neurologist. Early diagnosis and treatment of ADHD might improve quality of life, prognosis and outcome in patients with CF.
M. Cohen-Cymberknoh, T. Tanny, H. Blau, D. Kadosh, H. Mussaffi, V. Nir, L. Bentur, D. Shoseyov, E. Kerem, I. Berger
a. Hadassah-Hebrew University Medical Center, CF Center, Jerusalem, Israel
b. Hadassah-Hebrew University, Jerusalem, Israel
c. Schneider Children's Medical Center, Graub CF Center, Petach Tikva, Israel
d. Rambam Medical Center, CF Center, Haifa, Israel;
e. Hadassah-Hebrew University Medical Center, Pediatric Neurology Unit, Jerusalem, Israel
Genotype-phenotype correlation in CF
In these studies we combine extensive phenotype definitions and collaboration with molecular biology research. The studies lead to better understanding of the molecular basis for disease variability in CF.
Prof. Eitan Kerem with collaboration of Prof. Batsheva Kerem at the Hebrew University.
Inherited and clinical risk factors affecting the prognosis of CF
Researcher: Prof. Eitan Kerem
Use of nasal potential difference measurements to diagnose patients with atypical and questionable CF disease
Correction of defective CFTR function in patients carrying stop mutations. In these studies we measure nasal potential difference in CF patients before and after topical gentamicin administration.
Prof. Michael Wilschanski
Prof. Eitan Kerem
Oxidants status and Antioxidants in CF
In the past years there is increasing interest in antioxidants and oxidative stress in chronic diseases. In CF an increased oxidative stress was found and low levels of different antioxidants. We are measuring the influence of a pulmonary exacerbation on the oxidative stress. Our aim is to support our patients with the proper amount of antioxidants during an exacerbation to prevent further damage to the lungs.
Mrs. Hila Weisberg
Dr. Roni Cohen (Hebrew University)
Dr. Nachum Vaisman
Prof. Michael Wilschanski
Prof. Eitan Kerem
Osteoporosis in CF
Recently many patients with CF where diagnosed with osteopenia or osteoporosis. All our patients over 6 years are being screened in DXA (hologic) in these days and go through different biochemical tests. We hope to help clarifying the mechanism for bone depletion in CF.
Prof. Eitan Kerem
Patients who are interested to participate in the studies after discussing this with their CF center physician are welcome to call Prof. Eitan Kerem.