A Rare Case of Pulmonary Hypertension, Misdiagnosed as Interstitial Lung Disease: Pulmonary Capillary Hemangiomatosis.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. We reported a histologically confirmed PCH in a 42-yr-old lady. She presented a progressive dyspnea and cough after an upper respiratory tract infection. She had a leukocytosis and elevated ESR with negative collagen vascular laboratory results. Her chest imaging revealed mediastinal lymphadenopathy with bilateral ground glass opacities with increased interstitial septal thickening in lung parenchyma. Patient echocardiography showed severe right ventricular dilatation with a measured systolic pulmonary arterial pressure of about 105mmHg. Right heart catheterization revealed a mean pulmonary arterial pressure on 30 mmHg with a pulmonary capillary wedge pressure of about 7 mmHg. After starting anti PH treatment, the patient suffered a pulmonary edema and due to abnormal patient response to anti-PH therapies and radiologic findings. Finally, open lung biopsy was performed and showed features of pulmonary capillary hemangiomatosis.

Prevalence of Obstructive Sleep Apnea in a High-Risk Population Using the Stop-Bang Questionnaire in Tehran, Iran.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Despite its significant morbidities and mortality, the majority of patients with OSA remain undiagnosed. The epidemiology of OSA is well studied in Western countries, while there is scarce information on its epidemiology in other countries. We examined the prevalence of high-risk for OSA in a large urban region of Tehran, Iran. MATERIALS AND METHODS: We randomly selected 4021 individuals above 18 years in clusters from different districts of Tehran and surveyed them using the Stop-Bang questionnaire. The questionnaire also incorporated the demographic characteristics, education level, history of coronary artery disease and diabetes, and women's menopausal status. A score of 3 or higher on the Stop-Bang questionnaire indicated the high risk of OSA. RESULTS: The study population consisted of 2075 (51.6%) females and 1946 (48.4%) males, with the mean age of 40.88 years (SD, 15.4) and mean body mass index (BMI) of 26.18 kg/m2 (SD, 4.43). Overall, 51.4% of males and 26.5% of females (total, 1513; 38.6%) were classified in the high-risk group, according to the Stop-Bang questionnaire. The risk of OSA was directly correlated with BMI, advanced age, and history of cardiovascular diseases and diabetes. CONCLUSION: According to the Stop-Bang questionnaire, almost 1 out of every 3 individuals was classified in the high-risk group for OSA. Considering the significant morbidity and mortality of this disorder, it is considered a major health problem. Therefore, further detailed studies with confirmatory tests are recommended in order to plan strategies for the diagnosis, treatment, and rehabilitation of these patients.

Eighty Kilograms Weight Reduction in a Case of Obstructive Sleep Apnea with Several Comorbidities: Did the Conditions Improve?

Obstructive sleep apnea (OSA) together with metabolic disorders is common in severely obese patients. Weight reduction is considered as a treatment modality in these cases while few of them can succeed in considerable weight loss. Here, we present a severely obese man with body mass index of 54 suffered from OSA, type 2 diabetes, hypothyroidism, and hypertension. He intentionally lost 80 kilograms weight during the 2-year follow-up. Diabetes and hypertension completely resolved with considerable improvement in OSA syndrome after this huge weight reduction.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Sleep-disordered breathing as presenting manifestation of Chiari type I malformation: a case report.

Chiari Type I malformation (CM-I) is a rare disorder with displaced cerebellar tonsils through foramen magnum. Here we present a 30-year-old man with severe central and obstructive sleep apneas as presenting manifestations of CM-I. The patient underwent neurosurgery and the follow-up polysomnography revealed the resolution of central apnea while obstructive apnea remained unchanged. Central sleep apnea (CSA) could be associated with an underlying pathology; thus, further investigation is recommended in affected subjects.

Evaluation of bronchoscopy complications in a tertiary health care center.

BACKGROUND: Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. This study was performed to determine the complications of bronchoscopy in a tertiary health-care center. MATERIALS AND METHODS: This study had as descriptive cross sectional design. Four hundred adult patients between 16 to 85 years, who underwent bronchoscopy with a same method and same device and had no underlying disease, were consecutively enrolled. RESULTS: Bronchoscopy complications were seen in 13 patients (3.25%) including bleeding (four cases), pneumothorax (three cases), collapse (four cases), and infection (two cases). There was no association between complications and age, sex, bronchoscopy indications and findings (P > 0.05). CONCLUSION: According to the obtained results, it may be concluded that bronchoscopy can be performed safely whenever indicated. Complications occurred were minor and self limiting.

Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds.

Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor ß1 (IL-12Rß1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.

Evaluation of maximum O2 consumption: using ergo-spirometry in severe heart failure.

Although sport-physiologists have repeatedly analyzed respiratory gases through exercise, it is relatively new in the cardiovascular field and is obviously more acceptable than standard exercise test, which gives only information about the existence or absence of cardiovascular diseases (CVDs). Through the new method of exercise test, parameters including aerobic and anaerobic are checked and monitored. 22 severe cases of heart failure, who were candidates of heart transplantation, referring to Massih Daneshvari Hospital in Tehran from Nov. 2007 to Nov. 2008 enrolled this study. The study was designed as a cross-sectional performance and evaluated only patients with ejection fraction less than 30%. O2 mean consumption was 6.27±4.9 ml/kg/min at rest and 9.48±3.38 at anaerobic threshold (AT) exceeding 13 ml/kg/min in maximum which was significantly more than the expected levels. Respiratory exchange ratio (RER) was over 1 for all patients. This study could not find any statistical correlations between VO2 max and participants' ergonomic factors such as age, height, weight, BMI, as well as EF. This study showed no significant correlation between VO2 max and maximum heart rate (HR max), although O2 maximum consumption was rationally correlated with expiratory ventilation. This means that the patients achieved maximum ventilation through exercise in this study, but failed to have their maximum heart rate being led probably by HF-induced brady-arrhythmia or deconditioning of skeletal muscles.

Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency.

ISG15 is an interferon (IFN)-α/ß-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity.

Disseminated Mycobacterium kansasii in an HIV-negative patient.

Disseminated Mycobacterium kansasii infection is a rare infection in non-HIV patients. This research has uncovered a very rare manifestation of disseminated M. kansasii infection in a non-HIV patient with lung and pericardial involvement.

Predicted values of cardiopulmonary exercise testing in healthy individuals (a pilot study).

BACKGROUND: Cardiopulmonary exercise testing evaluates the ability of one's cardiovascular and respiratory system in maximal exercise. This was a descriptive cross-sectional pilot study conducted at Masih Daneshvari Hospital in order to determine predicted values of cardiopulmonary exercise testing in individuals with normal physical activity patterns. MATERIALS AND METHODS: Thirty four individuals (14 women, 20 men) between 18-57 years of age were chosen using simple sampling method and evaluated with an incremental progressive cycle-ergometer test to a symptom-limited maximal tolerable work load. Subjects with a history of ischemic heart disease, pulmonary disease or neuromuscular disease were excluded from the study. Smokers were included but we made sure that all subjects had normal FEV1 and FEV1/FVC. This study aimed to compare measured values of VO2, VCO2, VO2/Kg, RER, O2pulse, HRR, HR, Load, Ant, BF, BR, VE, EQCO2, and EQO2 with previously published predicted values. RESULTS: We found that our obtained values for VO2 max, HRR max and HR max were different from standard tables but such difference was not observed for other understudy variables. Multiple linear regression analysis was done for height, weight and age (due to the small number of samples, no difference was detected between males and females). VO2 max and load max had reverse correlation with age and direct correlation with weight and height (P < 0.05) but the greatest correlation was observed for height. CONCLUSION: Due to the small number of samples and poor correlations it was not possible to do regression analysis for other variables. In the next study with a larger sample size predicted values for all variables will be calculated. If the future study also indicates a significant difference between the predicted values and the reference values, we will need standard tables made specifically for our own country, Iran.

Lethal tuberculosis in a previously healthy adult with IL-12 receptor deficiency.

A 33-year-old man was admitted in hospital due to fever, generalized lymphadenopathy, and hepatosplenomegaly. He had a history of anti-tuberculosis treatment in the previous 3 years. Despite normal chest radiograph, a sputum sample was smear-positive for acid-fast bacilli, and polymerase chain reaction was positive for Mycobacterium tuberculosis complex. Drug susceptibility test revealed resistance to isoniazid and rifampin. Evaluation of the patient's immune system revealed IL-12Rß1 deficiency. The patient died of disseminated tuberculosis (TB), despite appropriate antibiotic treatment. This is the first IL-12 receptor-deficient patient presenting with disseminated TB in adulthood, without any previous relevant medical history. This diagnosis should be considered in selected adult patients with unexplained, overwhelming TB. IL-12Rß1 deficiency is a genetic etiology of severe TB in adults and should be considered in adult patients with disseminated TB.

Revisiting human IL-12Rß1 deficiency: a survey of 141 patients from 30 countries.

Interleukin-12 receptor ß1 (IL-12Rß1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rß1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.

Primary immune deficiencies presenting in adults: seven years of experience from Iran.

Primary immunodeficiencies (PIDs) are not solely diseases of childhood. We describe the clinical presentation and outcome for 55 adult patients with previously unrecognized PIDs. This series provides unique data regarding PIDs presenting in adulthood, and serves as a timely reminder that physicians must consider the diagnosis of PIDs in their adult patients. Using the experience gained from these patients, we outline key "warning signs" suggestive of an underlying PID. Only through increased physician awareness will patients with PIDs receive timely diagnosis and optimal management.

Inherited disorders of the IL-12-IFN-gamma axis in patients with disseminated BCG infection.

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN-gamma circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN-gamma receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations.

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.