Heather J. Zar

Global strategy for asthma management and prevention: GINA executive summary

Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled “A Global Strategy for Asthma Management and Prevention”, first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that “it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained,” and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient–care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.

Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study

BACKGROUND For microbiological confirmation of diagnosis of pulmonary tuberculosis in young children, sequential gastric lavages are recommended; sputum induction has not been regarded as feasible or useful. We aimed to compare the yield of Mycobacterium tuberculosis from repeated induced sputum with that from gastric lavage in young children from an area with a high rate of HIV and tuberculosis. METHODS We studied 250 children aged 1 month to 5 years who were admitted for suspected pulmonary tuberculosis in Cape Town, South Africa. Sputum induction and gastric lavage were done on three consecutive days according to a standard procedure. Specimens were stained for acid-fast bacilli; each sample was cultured singly for M tuberculosis. FINDINGS Median age of children was 13 months (IQR 6-24). A positive smear or culture for M tuberculosis was obtained from 62 (25%) children; of these, 58 (94%) were positive by culture, whereas almost half (29 [47%]) were smear positive. Samples from induced sputum and gastric lavage were positive in 54 (87%) and 40 (65%) children, respectively (difference in yield 5.6% [1.4-9.8%], p=0.018). The yield from one sample from induced sputum was similar to that from three gastric lavages (p=1.0). Microbiological yield did not differ between HIV-infected and HIV-uninfected children (p=0.17, odds ratio 0.7 [95% CI 0.3-1.3]). All sputum induction procedures were well tolerated; minor side-effects were increased coughing, epistaxis, vomiting, or wheezing. INTERPRETATION Sputum induction is safe and useful for microbiological confirmation of tuberculosis in young children. This technique is preferable to gastric lavage for diagnosis of pulmonary tuberculosis in both HIV-infected and HIV-uninfected infants and children.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study

BACKGROUND WHO recommends that Xpert MTB/RIF replaces smear microscopy for initial diagnosis of suspected HIV-associated tuberculosis or multidrug-resistant pulmonary tuberculosis, but no data exist for its use in children. We aimed to assess the accuracy of the test for the diagnosis of pulmonary tuberculosis in children in an area with high tuberculosis and HIV prevalences. METHODS In this prospective, descriptive study, we enrolled children aged 15 years or younger who had been admitted to one of two hospitals in Cape Town, South Africa, with suspected pulmonary tuberculosis between Feb 19, 2009, and Nov 30, 2010. We compared the diagnostic accuracy of MTB/RIF and concentrated, fluorescent acid-fast smear with a reference standard of liquid culture from two sequential induced sputum specimens (primary analysis). RESULTS 452 children (median age 19·4 months, IQR 11·1-46·2) had at least one induced sputum specimen; 108 children (24%) had HIV infection. 27 children (6%) had a positive smear result, 70 (16%) had a positive culture result, and 58 (13%) had a positive MTB/RIF test result. With mycobacterial culture as the reference standard, MTB/RIF tests when done on two induced sputum samples detected twice as many cases (75·9%, 95% CI 64·5-87·2) as did smear microscopy (37·9%, 25·1-50·8), detecting all of 22 smear-positive cases and 22 of 36 (61·1%, 44·4-77·8) smear-negative cases. For smear-negative cases, the incremental increase in sensitivity from testing a second specimen was 27·8% for MTB/RIF, compared with 13·8% for culture. The specificity of MTB/RIF was 98·8% (97·6-99·9). MTB/RIF results were available in median 1 day (IQR 0-4) compared with median 12 days (9-17) for culture (p<0·0001). INTERPRETATION MTB/RIF testing of two induced sputum specimens is warranted as the first-line diagnostic test for children with suspected pulmonary tuberculosis. FUNDING National Institutes of Health, the National Health Laboratory Service Research Trust, the Medical Research Council of South Africa, and Wellcome Trust.

Global Strategy for the Diagnosis and Management of Asthma in Children 5 Years and Younger

Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity from chronic disease as measured by school absences, emergency department visits, and hospitalions 1 . During the past two decades, many scientific advances have improved our understanding of asthma and our ability to manage and control it effectively. However, in children 5 years and younger, the clinical symptoms of asthma are variable and non‐specific. Furthermore, neither airflow limitation nor airway inflammation, the main pathologic hallmarks of the condition, can be assessed routinely in this age group. For this reason, to aid in the diagnosis of asthma in young children, a symptoms‐only descriptive approach that includes the definition of various wheezing phenotypes has been recommended 2 . In 1993, the Global Initiative for Asthma (GINA) was implemented to develop a network of individuals, organizations, and public health officials to disseminate information about the care of patients with asthma while at the same time assuring a mechanism to incorporate the results of scientific investigations into asthma care. Since then, GINA has developed and regularly revised a Global Strategy for Asthma Management and Prevention. Publications based on the Global Strategy for Asthma Management and Prevention have been translated into many different languages to promote international collaboration and dissemination of information.

International consensus on (ICON) pediatric asthma

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re‐evaluate and fine‐tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype‐specific treatment choices; however, this goal has not yet been achieved.

Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial

Objectives To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV. Design Two centre prospective double blind placebo controlled trial. Participants Children aged ≥8 weeks with HIV. Interventions Isoniazid or placebo given with co-trimoxazole either daily or three times a week. Setting Two tertiary healthcare centres in South Africa. Main outcome measures Mortality, incidence of tuberculosis, and adverse events. Results Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group. Conclusions Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis. Trial registration. Clinical Trials NCT00330304

Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III.

Phase I of the International Study of Asthma and Allergies in Childhood has provided valuable information regarding international prevalence patterns and potential risk factors in the development of asthma, allergic rhinoconjunctivitis and eczema. However, in Phase I, only six African countries were involved (Algeria, Tunisia, Morocco, Kenya, South Africa and Ethiopia). Phase III, conducted 5–6 years later, enrolled 22 centres in 16 countries including the majority of the centres involved in Phase I and new centres in Morocco, Tunisia, Democratic Republic of Congo, Togo, Sudan, Cameroon, Gabon, Reunion Island and South Africa. There were considerable variations between the various centres of Africa in the prevalence of the main symptoms of the three conditions: wheeze (4.0–21.5%), allergic rhinoconjunctivitis (7.2–27.3%) and eczema (4.7–23.0%). There was a large variation both between countries and between centres in the same country. Several centres, including Cape Town (20.3%), Polokwane (18.0%), Reunion Island (21.5%), Brazzaville (19.9%), Nairobi (18.0%), Urban Ivory Coast (19.3%) and Conakry (18.6%) showed relatively high asthma symptom prevalences, similar to those in western Europe. There were also a number of centres showing high symptom prevalences for allergic rhinoconjunctivitis (Cape Town, Reunion Island, Brazzaville, Eldoret, Urban Ivory Coast, Conakry, Casablanca, Wilays of Algiers, Sousse and Eldoret) and eczema (Brazzaville, Eldoret, Addis Ababa, Urban Ivory Coast, Conakry, Marrakech and Casablanca).

Aetiology and outcome of pneumonia in human immunodeficiency virus-infected children hospitalized in South Africa.

To determine the aetiology and outcome of pneumonia in human immunodeficiency virus (HIV)‐infected children, we prospectively investigated 250 children hospitalized with pneumonia who were known or clinically suspected to be HIV‐positive, or who required intensive care support in Cape Town, South Africa. Blood culture, induced sputum or bronchoalveolar lavage nasopharyngeal aspirate and gastric lavage were performed. Of the total, 151 children (60.4%) were HIV‐infected. Pneumocystis carinii pneumonia (PCP), occurring in 19 (7.6%) children (15 HIV‐positive), was the AIDS‐defining infection in 20.3%. The incidence and type of bacteraemia (14.3%) were similar in HIV‐positive and HIV‐negative patients; S. pneumoniae (5%) and S. aureus (2%) were the predominant isolates. Sputum or BAL cultures yielded bacteria in 145 of 243 (60%) specimens; viruses were cultured in 37 (15.2%). Bacterial prevalence (including M. tuberculosis in 8%) and anti‐microbial resistance did not differ by HIV status except for S. aureus which was more common in HIV‐infected children. Thirty‐one (20%) HIV‐positive and 8 (8%) HIV‐negative children died [RR 1.16 (95% CI 1.05–1.28), p= 0.008]; using multiple logistic regression, PCP was the only risk factor for mortality (p= 0.03).

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa

BACKGROUND Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children. AIMS To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children. SUBJECTS AND METHODS 149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrolment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis. RESULTS Sputum induction was successfully performed in 142 of 149 children.M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosiswas cultured in 10 of 100 HIV infected children compared to six of 42 HIV uninfected children (p = 0.46). CONCLUSION Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.