Fatemeh Fattahi

Inheritance Pattern and Clinical Aspects of 93 Iranian Patients with Chronic Granulomatous Disease

BackgroundChronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran.MethodsClinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families.ResultsMost of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p < 0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations.ConclusionsAlthough XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.

Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study

BackgroundThe pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated.MethodsFactors related to the presence of atopy (positive phadiatop) in 1277 mild-to-moderate COPD patients participating in EUROSCOP were analysed using regression analysis. Incidence and remission of respiratory symptoms during 3-year follow-up were analysed using generalised estimating equations models, and association of atopy with lung function decline using linear mixed effects models.ResultsIndependent predisposing factors associated with the presence of atopy were: male gender (OR: 2.21; 95% CI: 1.47–3.34), overweight/obese (OR: 1.41; 95% CI: 1.04–1.92) and lower age (OR: 0.98; 95% CI: 0.96–0.99). Atopy was associated with a higher prevalence of cough (OR: 1.71; 95% CI: 1.26–2.34) and phlegm (OR: 1.50; 95% CI: 1.10–2.03), but not with lung function levels or FEV1 decline. Atopic COPD patients not treated with budesonide had an increased incidence of cough over time (OR: 1.79, 95% CI: 1.03–3.08, p = 0.038), while those treated with budesonide had increased remission of cough (OR: 1.93, 95% CI: 1.11–3.37, p = 0.02) compared to non-atopic COPD patients.ConclusionsAtopic COPD patients are more likely male, have overweight/obesity and are younger as compared with non-atopic COPD patients. Atopy in COPD is associated with an increased incidence and prevalence of respiratory symptoms. If atopic COPD patients are treated with budesonide, they more often show remission of symptoms compared to non-atopic COPD patients who are treated with budesonide. We recommend including atopy in the diagnostic work-up and management of COPD.

Adverse Drug Reactions in Hospitalized Children in a Department of Infectious Diseases

A problem of drug therapy, one that confronts primary care physicians on a daily basis, is the risk of adverse drug reactions (ADRs). The World Health Organization (WHO) definition of an ADR, which has been in use for about 30 years, is “a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function.” Thus, this definition excludes adverse events caused by errors in drug administration or noncompliance (taking more or less of a drug than the prescribed amount). Using this conservative definition avoids overestimating the ADR rate. ADRs are a major and important health care problem. The percentage of patients experiencing an ADR during hospitalization has been reported to range from 1.5% to 35%. Also, the reported frequencies of hospital admissions attributed to ADRs vary from 0.1% to 16.8%. Several characteristics, such as a history of a previous ADR, duration of hospital stay, and liver or renal disease, have been suggested as risk factors for the development of ADRs. Although many ADRs are mild and disappear when the drug is stopped or the dose is reduced, others are serious, last longer, and are occasionally life threatening. It is usually stated that the frequency of ADRs is higher in adults than in children. A meta-analysis study reported ADR incidence among hospitalized children from 4.37% to 16.78%, with an estimated mean of 9.53%. This study also reported incidence of pediatric hospital admissions related to ADRs from 0.59% to 4.1%, with a weighted mean of 2.09%. Several risk factors, including differences in drug metabolism, which can produce increased susceptibility to certain drugs, may account for the severity and specificity of ADRs in children. In this case, some organs may be very sensitive to side effects. On the other hand, developmental processes in children may be susceptible to certain agents, and a number of drugs used in pediatric diseases can produce specific ADRs. Other risk factors for ADRs in children include multiple drug exposure, complex multisystem illness, age younger than 12 months, and increase in dose by parents or prescribers. Among the few studies in Iran, in a study on adult patients by Gholami and Shalviri in a department of infectious diseases, approximately 16.8% of hospitalized patients had at least 1 ADR. The aim of this study was to investigate and determine the frequency, severity, and characteristics of ADRs in children (14 years and younger) as a cause of admission to a children’s hospital or occurring during BRIEF REPORTS/PEDIATRICS

Adverse drug reactions in patients in an Iranian department of internal medicine

Adverse drug reactions (ADRs) are a major cause of hospital admission and inpatient morbidity. The department of internal medicine is not an exception to this issue. This study was performed to determine the nature and frequency of ADRs in an internal medicine ward in Iran.

Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment.

Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder in which phagocytic leukocytes fail to generate superoxide (O(2)(-)) and antimicrobial oxidants. The therapeutic validity of interferon-gamma (IFN-γ) has been well established in CGD patients but its underlying mechanisms remain poorly understood. One probable mechanism has been suggested to be modulation of nitric oxide (NO) release from phagocytic cells. Herein, we investigated NO production from neutrophil cells in CGD patients on treatment with IFN-γ in vivo and in vitro. We measured NO levels in sera from 19 CGD patients (group I: 7 patients treated with TMP-SMX, group II: 12 patients treated with TMP-SMX and IFN-γ simultaneously) and healthy control individuals (8 cases). We also measured NO production from neutrophils in both patients groups as well as in control group after adding 100 U IFN-γ in vitro. Our results showed that there was a significant difference between the groups in the NO levels of serum; patients who received IFN-γ had significantly higher amount of NO than the other groups. Besides, NO levels increased significantly after adding 100 U IFN-γ in vitro in three studied groups, considerably in the patients on treatment with IFN-γ. As a brief conclusion, the effect of IFN-γ in increasing NO production is obvious. This could be an explanation for the therapeutic effect of IFN-γ in patients with CGD as NO acts as a bactericidal agent and plays a role in host defense mechanism instead of O(2)(-).

Authors’ response to Persson C: primary lysis/necrosis of eosinophils and clinical control of asthma.

We have read with great interest the comments by Dr Persson on our recent paper in Thorax, in which we showed that clinical control of asthma associated significantly with lower numbers of activated eosinophils in the bronchial wall, yet only weakly with sputum eosinophils. As the number of eosinophils in biopsies did not associate with clinical control of asthma, we speculated that activation of eosinophils (measured as eosinophil protein X (EXP)immunopositive pixels per area) in bronchial biopsies reflects the level of disease control better than the number of eosinophils itself. As lysis of activated eosinophils and degranulation of toxic eosinophil proteins may damage the surrounding tissue, Persson wondered whether EPX immunopositivity in our biopsies associated with epithelial fragility, particularly in uncontrolled asthma. In line with Persson’s hypothesis, the percentage of intact epithelium correlated negatively with EPX immunopositivity (Spearman’s r=−0.30, p=0.016), whereas there was no significant correlation with the number of eosinophils in bronchial biopsies (Spearman’s r=−0.12, p=0.35) (figure 1). This was not due to effects of current smoking, which is associated with increased epithelial cell proliferation, goblet cell hyperplasia, as well as with reduced eosinophil numbers in bronchial biopsies in asthma, since we excluded current smokers from our analysis. An additional regression model adjusted for inhaled corticosteroid use and atopy confirmed that loss of epithelial integrity and higher EPX immunopositivity are significantly associated with uncontrolled asthma, yet not with numbers of airway wall eosinophils (data not shown). Another question from Persson’s letter was whether free granules locate in close proximity of denuded epithelium. Unfortunately, this ‘geographical’ relationship is very difficult to quantify in a reliable way. Moreover, we believe this specific question could be better investigated prospectively using an allergen provocation model; collecting blood, biopsies and sputum at regular time points; similar to what has been done in the past by Aalbers et al. In our existing dataset, the dynamics of transepithelial migration of eosinophils (tissue-lumen correlations) cannot be investigated in a reliable way. In conclusion, our statistical analysis supports Persson’s hypothesis that ongoing lysis of activated eosinophils contributes to uncontrolled asthma. Our previous

Smoking and nonsmoking asthma: differences in clinical outcome and pathogenesis

Cigarette smoking in asthma is frequently present and is associated with worsening of symptoms, accelerated lung-function decline, a higher frequency of hospital admissions, a higher degree of asthma severity, poorer asthma control and reduced responsiveness to corticosteroids. Furthermore, it is associated with reduced numbers of eosinophils and higher numbers of mast cells in the submucosa of the airway wall. Airway remodeling is increased as evidenced by increased epithelial thickness and goblet cell hyperplasia in smoking asthmatics. The pathogenesis responsible for smoking-induced changes in airway inflammation and remodeling in asthma is complex and largely unknown. The underlying mechanism of reduced corticosteroid responsiveness is also unknown. This article discusses differences between smoking and nonsmoking asthmatics regarding the clinical expression of asthma, lung function, response to corticosteroids, airway inflammation and remodeling processes. Possible pathogenetic mechanisms that may explain the links between cigarette smoking and changes in the clinical expression of asthma will be discussed, as well as the beneficial effects of smoking cessation.

Severe cutaneous reactions caused by barbiturates in seven Iranian children

Background  The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates.

Lethal toxic encephalopathy due to childhood shigellosis or Ekiri syndrome

Lethal toxic encephalopathy due to shigellosis or Ekiri syndrome is a rare complication of shigellosis with a high fatality rate. Data are very limited on factors that can predict this encephalopathy, so we evaluated clinical and laboratory characteristics for these patients. In this study children with extreme toxicity and convulsions followed by rapid neurological deterioration resulting in brain edema and fatal outcome without sepsis and severe dehydration were selected as having lethal toxic encephalopathy. There were 1295 children with shigellosis during the 10 years of the study. Five children (0.4%) had lethal toxic encephalopathy due to shigellosis. Death occurred following rapid neurological detoriation resulting in brain edema despite intensive treatment. Evidence of brain edema may be a prediction factor for death. Early recognition of encephalopathy and measures to prevent brain edema may improve patient outcome.

Adverse drug and medical instrument reactions in a pediatric intensive care unit

Adverse drug reactions (ADRs) may cause a variety of symptoms and changes in laboratory values. According to the World Health Organization (WHO) definition, ADR is any noxious, unintended, and undesired effect of a drug, which occurs at doses used in human for prophylaxis, diagnosis, or therapy. It is estimated that ADRs occur in approximately 5% of patients taking a drug while ADRs causing hospital admission vary from 0.2 to 22%; the reported ADRs in hospitalized children incidence ranged from 4.37 to 16.78% among studies. Little information exist on the frequency and consequences of ADRs in general and surgical Pediatric Intensive Care Units (PICUs). The therapeutic activity in the ICUs is very important since the patients receive many drugs for their pathophysiological abnormalities and because these patients frequently experience acute organic disturbance that make them particularly susceptible to undesirable drug effect, a relatively high ADR frequency can be expected. In a study by Vargas et al., it has been estimated that 9.2% cases of ADR in ICU ward were most frequently caused by morphine hydrochloride as was shown in several other studies. Therefore, we studied prospectively all patients admitted to the Department of Pediatric ICU of Children’s Medical Center, Tehran, Iran to investigate and determine the frequency, seriousness, and characteristics of ADRs based on the ADR definition of the WHO. All included patients were treated with drugs. The mean stay of patients in PICU who did not develop any ADR was 4 days (in the range of 1–19 days) compared with 7.6 days in those patients who presented some ADRs (SD1⁄4 4.3) (Table 1). As can be seen, ceftriaxon (n: 115), calcium gluconate (n: 90), phenytoin (n: 74), and ampicilline (n: 65) were the main drugs prescribed. Of the 230 drug-treated patients, five (2.2%) experienced at least one symptom that was judged to be an ADR. In total, five reactions were judged to be drug