Israel Medical Association Journal

Background: Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.

Objectives: To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.

Methods: We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.

Results: The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.

Conclusions: All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.

Background: With the increased use of cannabis in the medicinal and recreational domains, it is becoming more important for physicians to better understand its harmful and beneficial effects. Although medical cannabis comes in several forms, the preferred route of administration is smoking or inhalation. After caring for three asthmatic patients who were treated with medical cannabis and who reported improvement in their symptoms, we decided to review the available data on the effects of medical cannabis on asthmatic patients.

Objectives: To review the known effects of medical cannabis on asthmatic patients.

Methods: A thorough search was conducted of the MEDLINE and PubMed databases as well as the internet for publications about the effects of medical cannabis on asthmatic patients.

Results: Cannabis has a bronchodilator effect on the airways and might have an anti-inflammatory effect on asthmatic patients. However, harmful effects on the lungs are mainly attributed to smoking and include airway irritation and the development of chronic bronchitis symptoms.

Conclusions: Cannabis has some benefit, yet there are many harmful effects on the lungs. Additional research is needed to determine the harmful effects of vaporizers as well as inhalers.

Background: Asthma is a common respiratory disease, which is linked to air pollution. However, little is known about the effect of specific air pollution sources on asthma occurrence.

Objective: To assess individual asthma risk in three urban areas in Israel characterized by different primary sources of air pollution: predominantly traffic-related air pollution (Tel Aviv) or predominantly industrial air pollution (Haifa bay area and Hadera). 

Methods: The medical records of 13,875, 16- 19-year-old males, who lived in the affected urban areas prior to their army recruitment and who underwent standard pre-military health examinations during 2012–2014, were examined. Nonparametric tests were applied to compare asthma prevalence, and binary logistic regressions were used to assess the asthma risk attributed to the residential locations of the subjects, controlling for confounders, such as socio-demographic status, body mass index, cognitive abilities, and education.

Results: The asthma rate among young males residing in Tel Aviv was 8.76%, compared to 6.96% in the Haifa bay area and 6.09% in Hadera. However, no statistically significant differences in asthma risk among the three urban areas was found in controlled logistic regressions (P > 0.20). This finding indicates that exposure to both industrial- and traffic-related air pollution is associated with asthma prevalence.

Conclusions: Both industrial- and traffic-related air pollution have a negative effect on asthma risk in young males. Studies evaluating the association between asthma risk and specific air pollutants (e.g., sulfur dioxide, particulate matter, and nitrogen dioxide) are needed to ascertain the effects of individual air pollutants on asthma occurrence. 

 

Background: Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. 

Objectives: To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department.

Methods: The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by metered dose inhaler (100 μg/puff) attached to a spacer device. The number of puffs was determined by severity of disease according to GINA recommendations. After 2 years the outcome and cost analysis were examined.

Results: During 3 years since the initial policy change 92.5% patients were treated with spacers throughout their hospital stay (emergency department and pediatric ward). Costs were reduced by an estimated 63%. 

Conclusions: In view of its many advantages the replacement of nebulizers by MDI+S for the treatment of acute asthma is feasible, if performed in collaboration with the staff, hospital authority and patients.

 

Studies of the respiratory effects of air pollution in Israel published in peer-reviewed journals have been infrequent. Most empiric evidence relates to the association between air pollution and childhood asthma; other air pollution effects on other illnesses are less thoroughly studied. Our evaluation provides a possible explanation for the quite contradictory results demonstrated in the various studies. Actual effect estimates appear to differ considerably, ranging from no air pollution effect to a reasonably strong association detected between PM10 and asthma. We attribute these discrepancies to different research methodologies and different types of data used in various studies.

Background: The efficacy of subcutaneous immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity has been demonstrated in several studies.

Objectives: To investigate the effectiveness and side effects of immunotherapy in Israel and the relationship between local and systemic side effects.

Methods: This retrospective study was based on patient records and a computerized database for drug dispensing over a 5 year period. Success was rated as partial or complete. Side effects were classified as local or systemic. Systemic side effects were further classified according to severity, as mild (cutaneous), moderate (respiratory symptoms), or severe (cardiovascular).

Results: Of the 135 patients on aero-allergen immunotherapy who reached maintenance, 120 (88.9%) exhibited complete or partial improvement and 15 (11.1%) did not improve. All of the 44 patients on hymenoptera immunotherapy reached effective maintenance doses. The mean percent side effects calculated per treatment (injection) were 2.49 for local and 1.58 for a systemic reaction during the build-up phase, and 1.13 and 1.12 during the maintenance phase, respectively. Rates of systemic reactions were 1.3% for cutaneous, 1.14% for respiratory and 0.97% for cardiovascular reactions during the build-up phase, and 1.11%, 0.53%, and 0.51% during the maintenance phase, respectively. The odds of systemic reactions were significantly higher in patients with local reactions both in the build-up phase (P = 0.03) and in the maintenance phase (P = 0.0003). The number of annual medications dispensed per patient decreased from 31.5 to 26.0 during the first year after reaching maintenance, and to 22.5 in the second year. Pharmaceutical costs were 67% lower 1 year after the start of the maintenance phase, compared to the year before the start of immunotherapy, and 63% lower in the second year (P = NS).

Conclusions: Immunotherapy was effective and safe. Recognizing the benefits and safety of immunotherapy is necessary for physicians and health authorities in order to provide better care for allergic patients.

Background: Mite allergy is an indoor allergen responsible for most respiratory allergies in the western world. Environmental control can modify disease activity in these patients.

Objectives: To examine the benefit of the Plasma Cluster^® device (Sharp, Japan) for inactivating and removing mites from the environment of patients diagnosed with either mite‑sensitive perennial allergic rhinitis or mite‑sensitive allergic asthma.

Methods: Patients with AR[1] (n=30) or AA[2] (n=10) were enrolled into a prospective open observational 8 week study. The first 2 weeks involved initial evaluation, the following 4 weeks consisted of active usage of the device, and the last 2 weeks were designated for follow‑up. Symptom scores (recorded daily by patients and during visits by physicians) were recorded and analyzed.

Results: Patients with AR experienced a significant (P < 0.05) reduction in nasal discharge, post‑nasal drip, nasal congestion, nasal itching, watery eyes, itchy eyes, headache, itchy ears, night disturbances and an improvement in general well‑being during the last 2 days of the study compared to baseline. Patients with AA reported significant (P < 0.05) reduction in dyspnea, wheezing and the need to avoid dust mites. There was a significant (P < 0.05) improvement in mean peak expiratory flow rate at study closure compared to baseline.

Conclusions: Short-term usage of the Plasma Cluster^® device resulted in considerable clinical improvement and increased peak expiratory flow rate in patients with AR or AA. The findings of this pilot study warrant longer and controlled studies to determine the value of this device in the treatment of various allergic disorders.

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA[1] and COPD[2], which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β[3] targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.

Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size. 

Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.

Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.

Objectives: To examine the relation between CmsIgE[1] and the probability of resolution of milk allergy.

Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.

Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.

Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.

Background: Subcutaneous allergen immunotherapy is effective in treating allergic airway disease. Disadvantages include immediate local and systemic adverse reactions and poor compliance.

Objectives: To obtain real-life efficacy and safety data through a prospective observational study of SIT[1] in the allergist's office.

Methods: We prospectively collected data from all patients with a diagnosis of allergic rhinitis and/or asthma and a specific immunoglobulin E-mediated sensitization to one or more aeroallergens who began SIT during the 2 year period 1 January 2005 to 31 December 2006. As part of the routine immunotherapy care patients were asked to complete a disease activity questionnaire before and yearly during the treatment. The primary outcome measure was the combined rhinitis and asthma symptoms scores. Data from patients completing at least 1 year of immunotherapy were analyzed.

Results: Altogether, 133 enrolled patients with a mean age of 22.7 years completed at least 1 year of SIT. The allergic rhinitis and asthma disease activity score decreased from a mean of 8.1 to 3.3 (rhinitis) and from 4.8 to 2.4 (asthma) on a 10 cm visual analogue scale after 1 year of SIT (P < 0.001 for all comparisons). Rhinitis medication use in all patients and asthma medication use in asthmatics decreased significantly. Mild local adverse reactions were almost universal. There were 11 patients (8%) who developed 14 immediate systemic, mild to moderate reactions. All reactions were successfully treated in the clinic; none required additional observation or hospitalization.

Conclusions: In the hands of experienced allergists subcutaneous allergy immunotherapy is a safe and efficacious option for patients with allergic rhinitis and asthma.