What does STOP-IgAN tell us about how to treat IgA nephropathy?

Bronchoesophageal fistulae are a rare complication of tuberculosis. Traditionally they are managed by either thoracotomy with resection and closure of the fistulous tract or by taking a more conservative approach of giving standard treatment for tuberculosis while ensuring nutritional support through a nasogastric tube. We report a young student with disseminated tuberculosis complicated by a bronchoesophageal fistula. He was managed conservatively with anti-tuberculous chemotherapy and nutrition administered through a percutaneous endoscopic gastrostomy tube. This approach was associated with a relatively good quality of life and he was able to pursue his studies uninterrupted at the local university.

Performance of CURB-65 and CURB-age in community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is common and associated with significant mortality. In this study, we validated a newly proposed severity assessment rule for CAP, CURB-age, and also compared with to the currently recommended criteria in UK, CURB-65. METHODS: We conducted a prospective study in three hospitals in Norfolk and Suffolk, UK. One hundred and ninety patients were included and followed up for 6 weeks. RESULTS: Of 190 patients, 100 were men (53%). The age range was 18-101 years (median 76 years). Sixty-five (34%) had severe pneumonia by CURB-65 and 54 (28%) had severe pneumonia by CURB-age. There were 54 deaths during follow-up. There were 32 deaths (50%) in severe and 22 deaths (18%) in non-severe group by CURB-65. There were 27 deaths each in both the groups by CURB-age (50% of severe cases and 20% of non-severe cases). For CURB-65, sensitivity, specificity, and positive and negative predictive values were 59.3% (45.0-72.4), 75.7% (67.6-82.7), 49.2% (36.6-61.9) and 82.4% (74.6-88.6), respectively. For CURB-age, the respective values were 50.0% (31.1-63.9), 80.1% (72.4-86.5), 50.0% (36.1-63.9) and 80.1% (72.4-86.5). Exclusion of patients aged < 65 years did not alter the results. CONCLUSIONS: Despite better specificity in correctly identifying 6-week mortality for CAP, CURB-age appears to be less sensitive than CURB-65. Our findings further assure the usefulness of CURB-65 for predicting mortality in CAP.

Inhaled foreign bodies in adolescents and adults.

BACKGROUND: Accidental foreign body inhalation is not uncommon. The incidence is high in children, especially the very young ones. We evaluated the management of inhaled foreign bodies in an adult respiratory medical unit, highlighting circumstances leading to inhalation, associated complications and difficulties encountered at bronchoscopic retrieval. METHODS: We reviewed all cases of inhaled foreign bodies presenting over a period of 12 years (1991-2003). RESULTS: 5 of 8 cases were teenagers whereas 3 were aged over 55 years. The older patients had co-morbidities and had aspirated food particles. In 2 cases, a bronchoscopy was performed primarily to exclude lung cancer, and the discovery of a foreign body was a surprise. Pulmonary complications related to foreign body inhalation were common among this group. All 5 teenage patients presented after inhalation of small objects. 4 patients from the teenage group had general anaesthesia; in 2 of them a laryngeal mask airway was employed, whilst 2 had endotracheal intubation. Only one patient was given a rigid bronchoscopy following failure of the fiberoptic instrument. Difficulties at retrieval of foreign body were frequently encountered. CONCLUSIONS: In the adolescent and adult patients, most inhaled foreign bodies are retrievable by flexible bronchoscopy. However, facilities for rigid bronchoscopy should be available as a back-up. Pulmonary complications are common after foreign body inhalation especially in the older patients. Difficulties at bronchoscopic removal may occur due to late presentation or to the site and/or position of the foreign body within the tracheobronchial tree.

Empirical treatment for tuberculosis: survey of cases treated over 2 years in a London area.

OBJECTIVE: To determine factors influencing the decision to treat tuberculosis empirically and its outcome. METHODS: A retrospective survey was done to assess the factors influencing the decision to treat tuberculosis empirically and the effectiveness of such treatment, within a London area. Data on tuberculosis cases treated during 1995-96 (n = 218) was collected and analysed. RESULTS: One hundred and fifty-eight (72.5%) cases of tuberculosis were treated empirically, that is, in the absence of positive smear or histology. Factors suggesting tuberculosis were clinical suspicion, abnormal radiology, elevated Erythrocyte Sedimentation Rate (ESR) and/or C-reactive Protein (CRP), grade 3 or 4 Heaf test, contact or family history, and Heaf conversion. Significantly more Asian [79 of 105 (75.2%); p < 0.02] and African patients [61 of 81 (75.3%); p < 0.05] were treated empirically as compared to West European patients [14 of 28 (50%)]. Based on logistic regression, any non-European ethnicity carried a significant risk for being treated empirically [OR: 2.7, CI: 1.7-20.8; p < 0.05]. Patients requiring revision of diagnosis (n = 9) were older [55.7 +/- 10.1 vs 32.8 +/- 16.0 years; p < 0.001]; 6 of them had neoplastic conditions. CONCLUSION: In this survey, frequent use of empirical treatment for tuberculosis in non-European patients reflects the physicians' high index of suspicion. Although such therapy is justifiable in selected cases, the proportion requiring revision of diagnosis may be reduced by more thorough investigation, especially in older patients.

Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study.

BACKGROUND: Atopy is defined as the genetic propensity to develop immunoglobulin E antibodies in response to exposure to allergens and assessed by skin prick test responses to common allergens. Although it is generally agreed that atopy is an important risk factor for allergic diseases such as asthma, rhinitis, and eczema, the extent to which atopy accounts for these diseases is controversial. OBJECTIVE: We aim to describe the prevalence of sensitization to common allergens and investigate the degree of association of atopy (as defined by positive skin prick test to 1 or more common allergens) to asthma, rhinitis, and eczema in a birth cohort at the age of 4 years. METHODS: A birth cohort of 1456 children was recruited over a 14-month period (1989-1990). These children have been seen previously at 1 and 2 years of age. At 4 years, 1218 children were reviewed and an interview was administered or postal questionnaire was completed for the presence of allergic diseases (asthma, rhinitis, and eczema). Additionally, in 981 children, skin prick tests with a battery of 12 common allergens were performed. Allergens were house dust mite (Dermatophagoides pteronyssimus), grass pollen mix, cat, dog, Alternaria alternata, Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut. A mean wheal diameter of at least 3 mm greater than the negative control was taken as positive. This analysis is confined to the 981 (67% of the original population) who also had skin prick tests to the standard battery. chi(2) tests were used to test the univariate association between each allergic disease and positive skin test. Multiple logistic regression analysis was performed to obtain the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the independent effect of sensitization to each allergen on allergic disease, adjusting for the effect of sensitization to other allergens. To ascertain how much of allergic disease is attributable to atopy, we estimated the population-attributable risk. This was calculated with the formula: P(R - 1) where R is the OR for the allergic disease under consideration and P is the proportion of atopy in children with that disease. RESULTS: Children who were skin prick-tested at 4 years were similar in most characteristics to the rest of the population, except that they had a higher prevalence of allergic disease. Allergic disorders (asthma, rhinitis, and eczema) were present in 276 (28.1%) of 981. One hundred ninety-two (19.6%) children were atopic (positive reaction to 1 or more allergens). Sensitization to inhalant allergens was relatively common (19.2%) as compared with food allergens (3.5%). House dust mite (11.9%), grass pollen (7.8%), and cat (5.8%) were the most common positive reactions. A test to the 4 most common allergens (house dust mite, grass pollen, cat, and A alternata) could detect 94% of the atopic children. Sensitization to the 4 most common allergens was strongly associated with the presence of allergic disorders. There was a graded effect with the potent allergens, such as house dust mite, having the greatest impact. For example, 50% of children sensitized to house dust mite had asthma as opposed to 44% sensitized to cat, 42% sensitized to grass pollen, and 32% sensitized to A alternata. Overall, 68.4% of children sensitized to house dust mite had asthma, eczema, and/or rhinitis. The respective figures for grass pollen, cat, and A alternata were 64.9%, 66.7%, and 57.4%. The proportion of children sensitized to cat was not higher in households with cat ownership (households with cats: 5.1% [19/374]; households without cats: 6.2% [36/580]; not significant [NS]). Similarly, no difference was seen in sensitization to dog in households with and without dogs (households with dogs: 1.8% [5/282]; households without dogs: 2.8% [19/673]; NS). Boys were atopic more often than girls at this age (male: 112 of 497 [22.5%] vs female: 80 of 484 [16.5%]; OR: 1.47, 95% CI: 1.07-2.02). Male preponderance was observed with most allergens, but this was statistically significant only for house dust mite (male: 75/497 [15.1%] vs female: 42/484 [8.7%]; OR: 1.87; CI: 1.25-2.79) and grass pollen (male: 51/497 [10.3%] vs female: 26/484 [5.4%]; OR: 2.01; CI: 1.23-3.29). An independent effect of allergen sensitization on asthma was observed only with house dust mite with an OR of 8.07 (CI: 4.60-14.14). The highest independent risk for rhinitis was sensitization to grass pollen (OR: 5.02; CI: 2.21-11.41), and for eczema, sensitization to peanut (OR: 4.65; CI: 1.02-21.34). The majority of children (98/192) were sensitized to >1 allergen. A graded effect was observed with the risk of allergic disease in the child increasing with the number of positive skin prick test reactions. This effect was consistent throughout the spectrum of allergic diseases (asthma, eczema, and rhinitis). (ABSTRACT TRUNCATED)

Reiter's syndrome following intravesical BCG immunotherapy.

A 71 year old woman developed conjunctivitis, asymmetrical oligoarthritis, and cystitis (Reiter's syndrome) secondary to intravesical BCG treatment for transitional cell carcinoma of the bladder. She received oral prednisolone, izoniazid, and pyridoxine and made a full recovery. Increasing use of BCG as immunotherapy will lead to an increase in the incidence of BCG associated reactive arthritis. Prompt recognition and early diagnosis will facilitate treatment and recovery.

Influence of smoking on asthmatic symptoms and allergen sensitisation in early childhood.

BACKGROUND: Apart from heredity, several early life environmental factors are implicated in the development of childhood asthma. Maternal smoking is believed to increase asthmatic symptoms but its influence on the development of allergen sensitisation is debatable. STUDY DESIGN: A whole population birth cohort was reviewed at ages 1, 2, and 4 years. Of 1218 children seen at 4 years, 981 (80.5%) were skin prick tested with a battery of common food and aeroallergens. Smoking history was recorded at birth and updated at each follow up and its impact on the development of asthma and allergen sensitisation in the children was assessed. RESULTS: Two hundred and fifty mothers smoked during pregnancy (20.5%) and 307 (25.2%) after childbirth. Maternal smoking in pregnancy was associated with low birth weight (mean (SD): 3.3 (0.5) v. 3.5 (0.5) kg; p<0.001). Smoking mothers were more often from lower social classes (31.8% v. 16%, p<0. 001) and they breast fed their babies for a shorter duration (8.5 (11.4) v. 16.6 (15.2) weeks; p<0.001). The difference in breast feeding duration was partly due to a higher proportion of smoking mothers who never breast fed their babies. Although at age 2 years asthmatic symptoms were associated with exposure to maternal tobacco smoke (odds ratio 2.2, 95% confidence interval 1.5 to 3.4; p<0.001), this association was lost by 4 years. However, maternal smoking was a significant risk factor in a subgroup of children with asthmatic symptoms but negative skin prick test. Maternal smoking did not increase allergen sensitisation at age 4 years. No effect of paternal smoking on asthma was observed in the children.

Egg allergy in infancy predicts respiratory allergic disease by 4 years of age.

Sensitization to hen's egg early in life has been proposed as a predictor for respiratory allergic disease during childhood. However, symptomatic egg allergy in infancy has not been studied in this context. In 1989, a cohort of consecutive births was recruited. Data on family history of atopy and environmental factors were collected. At 4 years of age, 1,218 children were seen of whom 981 were skin-prick tested with a range of food and aero-allergens. Of the 1,218 children, 29 (2.4%) had suffered symptomatic egg allergy (20 during infancy). Egg allergy in infancy was associated with increased respiratory (asthma, rhinitis) allergic disease (odds ratio [OR] 5.0, 95% confidence intervals [CI] 1.1-22.3; p < 0.05) at 4 years of age, with a positive predictive value (PPV) of 55.0%. The addition of infantile eczema to egg allergy increased the PPV to 80% whereas the addition of family history of atopy had no effect. Egg allergy also increased aero-allergen sensitization (OR 6.1, CI 1.1-37.5; PPV 61.1%; p < 0.05). As a predictor for respiratory allergic disease and aeroallergen sensitization, it carried a high specificity but poor sensitivity. Hence, egg allergy in infancy, especially when coexisting with eczema, increases respiratory allergic symptoms and aero-allergen sensitization in early childhood.

Elevated cord serum IgE increases the risk of aeroallergen sensitization without increasing respiratory allergic symptoms in early childhood.

BACKGROUND: Increasing prevalence of allergic disorders has focused attention on primary prevention. There is a need to improve the accuracy of early-life predictors of atopy so that the at-risk population can be accurately defined and preventive measures instituted. OBJECTIVE: The predictive capacity of elevated cord IgE, with or without family history of atopy, to allergic symptoms and skin prick test (SPT) sensitization is evaluated in a birth cohort followed up prospectively for 4 years. METHODS: A birth cohort of 1456 consecutively born children was recruited in 1989. Data were collected on family history of atopy and cord serum total IgE (cord IgE) was measured. Of these, 1218 children were seen in the clinic at 4 years to determine the development of symptoms and signs of allergic disease and 981 were skin tested to a range of common food and aeroallergens. RESULTS: Of 1218 children reviewed at age 4 years, 218 (17.8%) had symptoms of respiratory allergy and, of those skin tested (n = 981), 192 (19.6%) reacted positively. Twice as many children with elevated cord IgE (>/= 0.5 kU/L) at birth became sensitized to aeroallergens by age 4 years (34.8% vs 17.3%, P < 0. 001). Positive predictive value (PPV) of elevated cord IgE for the development of aeroallergen sensitization was better than that of family history of atopy (34.8 vs 22.6%). Combining paternal atopy with elevated cord IgE substantially increased the predictive capacity (PPV 77.8%). Cord IgE levels did not correlate with clinical asthma or rhinitis at age 4 years and PPV for allergic respiratory symptoms remained poor at all cutoffs. CONCLUSION: Cord IgE is better than family history for predicting atopy as defined by allergen sensitization and this predictive value can be further increased by combining cord IgE with paternal atopy.

The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study.

OBJECTIVES: A birth cohort was followed-up to age 4 years to record the development of allergic disorders and to study the influence of genetic and environmental factors. METHODS: Information on family history and environmental factors was obtained at birth, and serum cord IgE was measured. At age 4 years, 1218 children were reviewed. RESULTS: By age 4 years, 27% of the children had symptoms of allergic disease. Period prevalence of asthma increased from 8.7% in infancy to 14.9% at 4 years. Family history of atopy was the single most important risk factor for atopy in children. Sibling atopy was a stronger predictor of clinical disease than maternal or paternal atopy, whereas paternal atopy, male sex, and high cord IgE were significant for the development of allergen sensitization. Children of asthmatic mothers were three times more likely to have asthma (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.6-5.8) and rhinitis (OR: 2.9, CI: 1.1-7.4). Formula feeding before 3 months of age predisposed to asthma at age 4 years (OR: 1.8, CI: 1.2-2.6). The effect of maternal smoking on childhood wheeze seen at 1 and 2 years was lost by age 4, except for a subgroup with negative skin test responses (nonatopic asthma). Less than half (46%) of the infantile wheezers were still wheezing at 4 years of age. CONCLUSION: Family history of atopy remains the most important risk factor for atopy in children, but other markers can be identified with a potential for intervention at an early age.

Cohort study of peanut and tree nut sensitisation by age of 4 years.

OBJECTIVE: To determine the prevalence of sensitisation to peanuts and tree nuts in all children born during one year in one geographical area. DESIGN: Birth cohort study with structured review at ages 1, 2, and 4 years. SETTING: All children born on the Isle of Wight between January 1989 and February 1990. SUBJECTS: Of 1456 children originally included, 1218 were reviewed at age 4 years. Of these, 1981 had skin prick tests. MAIN OUTCOME MEASURES: Positive skin test results, clinical atopic disease, and risk factors for the development of atopy. RESULTS: 15 of 1218 (1.2%) children were sensitised to peanuts or tree nuts (13 to peanuts). Six had had allergic reactions to peanuts (0.5% of the population), one to hazelnuts, and one to cashew nuts; three had had anaphylactic reactions. Seven children had positive skin test results or detectable IgE to peanuts without clinical symptoms. Two children who reacted to peanut in infancy had lost their sensitivity by 4 years. Family history of atopy, allergy to egg (odds ratio 9.9, 95% confidence interval 2.1 to 47.9, and eczema (7.3, 2.1 to 26.1) were important predictors for peanut allergy. CONCLUSIONS: IgE mediated allergy to peanuts is common in early childhood. In many the allergy persists but a minority may develop tolerance.

Sensitization to Alternaria and Cladosporium by the age of 4 years.

Of 1218 children born on the Isle of Wight in 1989/90, and followed for atopy at age 4 years, 981 were skin-prick tested with a battery of allergens. Of these 61 (6%) reacted positively to Alternaria alternata and Cladosporium herbarum (47 to Alternaria, 21 to Cladosporium and seven to both). Twenty-four (39%) were asymptomatic (latent atopy) of which 12 had a single positive reaction either to Alternaria or Cladosporium. Asthma was the most common disease in children sensitized to moulds. Alternaria sensitization correlated positively with clinical diagnosis of asthma (P < 0.01), eczema (P < 0.001) and rhinitis (P < 0.05). Likewise, Cladosporium sensitivity correlated with a diagnoses of asthma, eczema and rhinitis (all P < 0.05). Age of the house correlated with reported damp and lack of central heating (both P < 0.001), but not with sensitization to moulds. An association between the presence of damp or age of the house and mould allergy was confounded by 21 children moving house in the first 4 years. Exposure to pets, passive tobacco smoking and season of birth had no bearing on mould sensitivity. At 4 years of age Alternaria and Cladosporium were the third most common causes of sensitization, i.e. after house dust mite and grass pollen.

Allergen avoidance in the primary prevention of atopy.

Atopy development cannot yet be predicted with certainty, and primary prophylaxis has to be directed at every 'at-risk' infant. However, substantial progress has been made in identifying environmental factors associated with allergic disorders. The process of sensitisation to common allergens may begin in utero. The influence of adjuvants, especially passive smoking, is considerable in individuals with established atopic disease. This article examines the role of intervention during pregnancy and the first year of life in the primary prevention of atopy and suggests a number of measures based on the current evidence.