Hamdan Al-Jahdali

Role of Transforming Growth Factor–β in Airway Remodeling in Asthma

TGF-β is one of the main mediators involved in tissue remodeling in the asthmatic lung. This profibrotic cytokine is produced by a number of cells, including macrophages, epithelial cells, fibroblasts, and eosinophils. High expression of TGF-β in patients with asthma was reported by many investigators. However, controversy remains whether the concentration of TGF-β correlates with disease severity. TGF-β is believed to play an important role in most of the cellular biological processes leading to airway remodeling. It was shown to be involved in epithelial changes, subepithelial fibrosis, airway smooth muscle remodeling, and microvascular changes. Here, sources of TGF-β, as well as its role in the development of airway remodeling, will be reviewed. Therapeutic strategies that modulate TGF-β will also be discussed.

CC and CXC Chemokines Induce Airway Smooth Muscle Proliferation and Survival

The increase in airway smooth muscle (ASM) mass is a major structural change in asthma. This increase has been attributed to ASM cell (ASMC) hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced, suggesting migration of smooth muscle cells toward the epithelium. Recent studies have suggested a role of chemokines in ASMC migration toward the epithelium; however, chemokines have other biological effects. The objective of the current study is to test the hypothesis that chemokines (eotaxin, RANTES, IL-8, and MIP-1α) can directly influence ASMC mass by increasing the rate of proliferation or enhancing the survival of these cells. Human ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8, or MIP-1α. To test for proliferation, matched control and stimulated ASMC were pulsed with [3H]thymidine, or ASMCs were stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V staining and flow cytometry. Expression of phosphorylated p42/p44 and MAPKs was assessed by Western blot. In a concentration-dependent manner, chemokines including eotaxin, RANTES, IL-8, and MIP-1α increased ASMC’s [3H]thymidine incorporation and DNA synthesis. IL-8, eotaxin, and MIP-1α decreased the rate of apoptosis of ASMCs compared with the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. Moreover, inhibition of p42/p44 MAPK phosphorylation reduced the level of chemokine-induced ASM proliferation. We conclude that chemokines might contribute to airway remodeling seen in asthma by enhancing the number and survival of ASMCs.

Bronchiolitis obliterans organizing pneumonia: Pathogenesis, clinical features, imaging and therapy review

Bronchiolitis obliterans organizing pneumonia (BOOP) was first described in the early 1980s as a clinicopathologic syndrome characterized symptomatically by subacute or chronic respiratory illness and histopathologically by the presence of granulation tissue in the bronchiolar lumen, alveolar ducts and some alveoli, associated with a variable degree of interstitial and airspace infiltration by mononuclear cells and foamy macrophages. Persons of all ages can be affected. Dry cough and shortness of breath of 2 weeks to 2 months in duration usually characterizes BOOP. Symptoms persist despite antibiotic therapy. On imaging, air space consolidation can be indistinguishable from chronic eosinophilic pneumonia (CEP), interstitial pneumonitis (acute, nonspecific and usual interstitial pneumonitis, neoplasm, inflammation and infection). The definitive diagnosis is achieved by tissue biopsy. Patients with BOOP respond favorably to treatment with steroids.Bronchiolitis obliterans organizing pneumonia (BOOP) was first described in the early 1980s as a clinicopathologic syndrome characterized symptomatically by subacute or chronic respiratory illness and histopathologically by the presence of granulation tissue in the bronchiolar lumen, alveolar ducts and some alveoli, associated with a variable degree of interstitial and airspace infiltration by mononuclear cells and foamy macrophages. Persons of all ages can be affected. Dry cough and shortness of breath of 2 weeks to 2 months in duration usually characterizes BOOP. Symptoms persist despite antibiotic therapy. On imaging, air space consolidation can be indistinguishable from chronic eosinophilic pneumonia (CEP), interstitial pneumonitis (acute, nonspecific and usual interstitial pneumonitis, neoplasm, inflammation and infection). The definitive diagnosis is achieved by tissue biopsy. Patients with BOOP respond favorably to treatment with steroids.

The calcified lung nodule: What does it mean?

The aim of this review is to present a pictorial essay emphasizing the various patterns of calcification in pulmonary nodules (PN) to aid diagnosis and to discuss the differential diagnosis and the pathogenesis where it is known. The imaging evaluation of PN is based on clinical history, size, distribution and the gross appearance of the nodule as well as feasibility of obtaining a tissue diagnosis. Imaging is instrumental in the management of PN and one should strive not only to identify small malignant tumors with high survival rates but to spare patients with benign PN from undergoing unnecessary surgery. The review emphasizes how to achieve these goals. One of the most reliable imaging features of a benign lesion is a benign pattern of calcification and periodic follow-up with computed tomography showing no growth for 2 years. Calcification in PN is generally considered as a pointer toward a possible benign disease. However, as we show here, calcification in PN as a criterion to determine benign nature is fallacious and can be misleading. The differential considerations of a calcified lesion include calcified granuloma, hamartoma, carcinoid, osteosarcoma, chondrosarcoma and lung metastases or a primary bronchogenic carcinoma among others. We describe and illustrate different patterns of calcification as seen in PN on imaging.

Severe sepsis and septic shock at the Hajj: etiologies and outcomes.

BACKGROUND The Hajj represents the largest mass migration on earth, during which several million Muslims travel across the planet to descend on specific holy sites at Makkah in the Hijaz area of the Kingdom of Saudi Arabia. Since sepsis syndrome is a major worldwide cause of morbidity and mortality we decided to study the incidence, etiologies, complications and outcome of severe sepsis and septic shock among Hajjees patients in two major intensive care units (ICUs) in Makkah for the Hajj season 2004. METHOD A prospective observational study was conducted during the 2004 Hajj season between 8 January and 21 February in two major hospitals in Makkah. RESULTS Severe sepsis and septic shock accounts for 25.4% of admission to the ICU during Hajj. The mean age of hajjees was 65.45 (+/-14.0) years. Chronic respiratory illness was the leading comorbidity present in more than 70% of hajjees and pneumonia was the leading cause of sever sepsis and septic shock. Gram-negative organisms were the most frequently isolated pathogen in this subset of patients. Acute renal failure is common among pilgrims who presented with septic shock, and carries high mortality. CONCLUSION Septic shock is a major cause of admission to the ICU during Hajj and carries a poor outcome. More studies are needed to evaluate modifiable factors that are associated with this high mortality.

Insomnia in chronic renal patients on dialysis in Saudi Arabia

Background Studies have shown that insomnia is a common sleep disorder among patients with end-stage renal disease (ESRD). This study aimed to assess the prevalence of insomnia in Saudi patients with ESRD who are on maintenance dialysis. Methods This was an observational cross-sectional study carried out over a period of five months in two hemodialysis centers in Saudi Arabia. To assess the prevalence of insomnia, we used the ICSD-2 definition. We also examined the association between insomnia and other sleep disorders, the underlying causes of renal failure, dialysis duration, dialysis shift, and other demographic data. Results Out of 227 enrolled patients, insomnia was reported by 60.8%. The mean patient age was 55.7 ± 17.2 years; 53.7% were male and 46.3% were female. Insomnia was significantly associated with female gender, afternoon hemodialysis, Restless Legs Syndrome, high risk for obstructive Sleep Apnea Syndrome and excessive daytime sleepiness (P-values: 0.05, 0.01, < 0.0001, < 0.0001, and < 0.0001, respectively). No significant association was found between insomnia and other variables, including BMI, smoking habits, underlying etiology of renal failure, dialysis duration, association with hemoglobin, ferritin, and phosphorus or dialysis adequacy as measured by the Kt/V index. Conclusion Insomnia is common in dialysis patients and was significantly associated with other sleep disorders. Greater attention needs to be given to the care of dialysis patients with regard to the diagnosis and management of insomnia and associated sleep disorders.

Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils

BackgroundSubepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood.ObjectiveIn this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines.MethodsEosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays.ResultsThe basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release.ConclusionsTh17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

Respiratory disorders in the Middle East: A review

The spectrum of pulmonary pathology in the Middle East is as versatile as its civilizations and cultures. In this review, we outline the key challenges confronting pulmonologists in the Middle East. We shed light on the diverse conditions commonly encountered in the region, from the centuries‐old illnesses of tuberculosis, to contemporary problems such as lung complications from chemical warfare. We specifically highlighted unique aspects related to respiratory illnesses in the Middle East, for example, climate factors in the desert region, cultural habits, for example, water‐pipe smoking and disorders unique to the region, such as Behçets disease. Pulmonologists are also faced with the consequences of modernization, including large immigrant population and associated social and health issues, rising incidence of obesity and sleep apnoea, and drug‐resistant tuberculosis. Tackling these health issues will require an integrated approach involving public health, primary care as well as specialist pulmonology input, taking into consideration the unique cultural and environmental factors to ensure effective management and compliance to medical care.

Imaging lung manifestations of HIV/AIDS.

Advances in our understanding of human immunodeficiency virus (HIV) infection have led to improved care and incremental increases in survival. However, the pulmonary manifestations of HIV/acquired immunodeficiency syndrome (AIDS) remain a major cause of morbidity and mortality. Respiratory complaints are not infrequent in patients who are HIV positive. The great majority of lung complications of HIV/AIDS are of infectious etiology but neoplasm, interstitial pneumonias, Kaposi sarcoma and lymphomas add significantly to patient morbidity and mortality. Imaging plays a vital role in the diagnosis and management of lung of complications associated with HIV. Accurate diagnosis is based on an understanding of the pathogenesis of the processes involved and their imaging findings. Imaging also plays an important role in selection of the most appropriate site for tissue sampling, staging of disease and follow-ups. We present images of lung manifestations of HIV/AIDS, describing the salient features and the differential diagnosis.

Pattern and risk factors for intentional drug overdose in Saudi Arabia

Background: Attempted suicide by intentional drug overdose is an understudied subject in Saudi Arabia. Saudi Arabia is an Islamic country where suicide or attempted suicide is strictly prohibited. Despite the strong religious and constitutional sanctions against suicide, cases of intentional drug overdose occasionally occur. Our study represents the first attempt to better understand and characterize this sensitive topic. Methods: Using a retrospective chart review of patients aged 12 years and over with a diagnosis of intentional drug overdose between 1997 and 1999, we studied the demographic characteristics, the risk factors, the most commonly used drugs, and the resulting morbidities and mortalities of study subjects. Results: Most of the patients were young (mean age 22 years, SD 4.6, range 15 to 40 years), and most were Saudi nationals (n = 76; 96%). Eighty percent of the patients were women. The occurrence of intentional drug overdose peaked during the month of September (that is, 20% of total cases). Previous suicide attempts, family conflicts, and psychiatric disorders represented significant risk factors. Single-agent overdose occurred in 30% of the patients, and most of the drugs used were prescribed medications (53%). Acetaminophen represented the most common drug (30%). While some patients required prolonged hospital stay or admission to the intensive care unit, no mortalities occurred. Conclusions: Intentional drug overdose is a relatively uncommon reason for hospital admission in Saudi Arabia. This study identifies certain risk factors relevant to the Saudi community and raises awareness about intentional drug overdose.