pulmonary function in non-atopic and atopic childhood asthma

Acta Pædiatrica ISSN 0803–5253

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Pulmonary function in non-atopic and atopic childhood asthmaJu Yin1, Andrew S Kemp1,2, Peter P van Asperen ([email protected])1,2

1.The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia2.Discipline of Paediatrics & Child Health, The Children’s Hospital at Westmead Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia

CorrespondenceProf. Peter van Asperen, Head, Department of Respiratory Medicine, The Children’sHospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia.Tel: 61-2-98453397 | Fax: 61-2-98453396 | Email: [email protected]

Received8 February 2006; revised 1 April 2007; accepted 3 April 2007

DOI:10.1111/j.1651-2227.2007.00342.x

Previous conclusions concerning pulmonary function innon-atopic and atopic asthma in childhood appear to differdepending on whether the cohorts studied are drawn fromthe community or clinic. In studies on community-based co-horts, Kelley et al. (1) found no differences in asthma sever-ity and pulmonary function and Kurukulaaratchy et al. (2)found that baseline spirometric parameters (FEV1, FVC orPEF) were not significantly different when comparing non-atopic and atopic children with asthma. In contrast, Oster-gaard (3) who identified 84 cases from an allergy clinic foundthat non-atopic asthmatics had significantly more hyperin-flation, reduced pulmonary function and more hospital ad-missions than atopic asthmatics. These observations raisequestions as to whether non-atopic asthma presenting tospecialist clinics differs from that detected in the commu-nity and whether it differs qualitatively from atopic asthma.In this study we compare pulmonary function in childrenwith non-atopic and atopic asthma presenting to a tertiaryhospital specialist clinic.

A retrospective case–control design in patients drawnfrom a specialist paediatric respiratory clinic was used.Asthma diagnosis was made by a paediatric respiratoryphysician. Allergen Skin Prick Tests (SPTs) and PulmonaryFunction Tests (PFTs) were performed in the respiratory lab-oratory between 1996 and 2006 and methodologies for theirperformance did not change during this period. We selected53 children with a diagnosis of asthma, who were non-atopicon SPTs and had had PFTs and age (±6 months) and gendermatched with 53 children with a diagnosis of asthma whowere atopic on SPTs and had had PFTs. The PFTs used forthe analysis were those performed at the same time as theSPTs in over 90% of the patients. PFTs were performed us-ing standardized spirometric techniques (4) with a VmaxSpirometer (Sensormedics 6200, Yorba Linda, CA) andbaseline forced vital capacity (FVC), forced expiratory vol-ume (FEV1), forced expiratory flow between 25% and 75%vital capacity (FEF 25–75) and peak expiratory flow (PEF)recorded as a percentage predicted (5). The FEV1/FVC ratiowas also calculated. SPTs were performed on nine inhalant

allergens extracts: grass mix, rye grass, English plantain, catpelt, dog hair, two house dust mite (HDM) species (Der-matophagoides pteronyssinus, Dermatophagoides farinae),cockroach mix and Alternaria (Hollister Stier, Spokane, WA,USA) as well as positive (histamine 10 mg/ml) and negative(saline) controls. Atopic subjects were defined as those whohad at least one positive reaction with a mean wheal diam-eter measuring 3 mm or more or 3 mm greater than a whealobtained with a negative control. Clinical information wasobtained from the subjects’ medical record after matching ofatopic with non-atopic subjects was complete. The study wasapproved as a medical record audit by the hospital’s ethicscommittee. Chi-square and independent sample t-tests weredetermined using SPSS 11.5. A p-value of 0.05 or less wasregarded as significant.

We matched age and sex of 53 non-atopic asthmatic chil-dren (median age 6.28 years, 58.5% male) with 53 childrenwith atopic asthma (median age 6.85 years, 58.5% male).Height (mean 126.79 cm vs. 124.58 cm), weight (median25.65 kg vs. 25.14 kg) and BMI (median 16.84 vs. 16.53)also did not differ significantly in children with non-atopicand atopic asthma. The 53 atopic children were positive tothe following allergens: HDM (92.5%), Alternaria (32.1%),cockroach (28.3%), cat (26.4%), rye grass (24.5%), grassmix (18.9%), plantain (15.1%) and dog (7.5%). Children withnon-atopic asthma had a higher prevalence of documentedbronchiolitis in infancy (13/53 vs. 4/53; p = 0.017), weremore likely to present initially with cough in the absence ofwheeze (16/47 vs. 8/46; p = 0.049) and were less likely tohave a history of atopic dermatitis ever (17/38 vs. 34/47; p =0.01). There was no difference between the age of onset ofasthma symptoms between the non-atopic and atopic groupwith 26 of 45 (58%) of the non-atopic group and 23 of 43(54%) of the atopic group developing symptoms in the first3 years of life. There was no difference in inhaled corticos-teroid (ICS) use at the time of presentation to the clinic, butthe non-atopic group was less likely to be treated in the ICSby the respiratory physician (27/52 vs. 40/53; p = 0.013).Overall, there were no significant differences for any of the

1088 C©2007 The Author(s)/Journal Compilation C©2007 Foundation Acta Pædiatrica/Acta Pædiatrica 2007 96, pp. 1088–1094

Yin et al. Pulmonary function and childhood asthma

Table 1 PFTs in children with atopic compared with non-atopic children

FVC FEV1 FEV1/FVC FEF 25–75 PEF(% pred.) (% pred.) (% pred.) (% pred.)

Non-atopic 100.71±24.56 99.92±28.93 88.69±7.75 93.96±32.58 119.36±59.80(n = 53)Atopic one allergen +ve 104.67±10.40 102.67±17.19 87.38±9.44 97.52±33.25 114.76±37.84(n = 21) (p = 0.337) (p = 0.686) (p = 0.544) (p = 0.676) (p = 0.746)Atopic >2 allergens +ve 94.53±12.70 87.25±16.09 83.16±7.96 76.81±26.56 105.22±35.94(n = 32) (p = 0.134) (p = 0.026) (p = 0.003) (p = 0.014) (p = 0.232)

parameters measured in the PFTs between the atopic andnon-atopic groups. However, on comparison of those withsensitization to a single inhalant allergen (n = 21, 19 HDM, 2Alternaria) with those with sensitization to multiple inhalantallergens, we found that those with multiple inhalant aller-gen sensitivities had significantly lower FEV1, FEV1/FVCand FEF 25–75% when compared to those with non-atopicasthma (Table 1). There were no significant differences inlung function between the non-atopic group and those withsensitization to a single inhalant allergen (Table 1).

In this population drawn from a specialist respiratoryclinic, non-atopic asthma was not a more severe disease thanatopic asthma and those with non-atopic asthma did notdiffer significantly in lung function from normals or thosesensitized to a single allergen. These findings are consistentwith the observations from community-based populations(1,2) that there were no major differences in the lung func-tion in the two groups, but differ from the observations ofOstergaard who found that non-atopic asthma had worselung function (3) and a poorer prognosis (6). It is notablethat Ostergaard’s cases had more hospital admissions forpneumonia and 5 of 72 went on to develop bronchiectasis(6) suggesting that this non-atopic asthma population con-tained a significant number of subjects with a propensity tosuppurative lower respiratory tract infection. In this con-text, it is of note that in a recent series of children withbronchiectasis half had a referral diagnosis of asthma (7).In contrast, in our study multiple allergen sensitization wasassociated with significantly worse lung function. This ob-servation is consistent with that of Ponsonby et al. (8) whofound greater wheeze frequency and hospital attendance in8- to 10-year-old children with atopic wheeze than in thosewith non-atopic wheeze and with the findings of Schwindtet al. (9) who found that a greater degree of atopy is associ-ated with increased asthma severity.

These observations raise the issue as to whether the air-ways inflammation in atopic asthma differs qualitatively innature from that in non-atopic asthma. There are com-mon features in the inflammatory response. Bronchial mu-cosal biopsy specimens from both atopic and non-atopicasthmatic subjects had increased numbers of cells express-ing IL-4 and IL-5 mRNA and protein (10). Eosinophiliccationic protein (ECP) (11) and serum tryptase (12), a mea-sure of mast cell activation, were increased to similar levelsin atopic and non-atopic asthma. Changes in ECP reflectingeosinophil activity were related to the severity of the asthma

rather than the presence of atopy (13). Thus, the inflamma-tory process may be qualitatively similar with a quantitativedifference depending on the level of allergen sensitization.

We conclude that in our population non-atopic asthmais not a more severe disease than atopic asthma. However,sensitization to multiple allergens is associated with reducedlung function suggesting that the degree of atopy as deter-mined by multiple allergen sensitization is a stronger deter-minant of airways pathology rather than sensitization to aparticular allergen such as HDM.

ACKNOWLEDGEMENTJu Yin, from Department of Respiratory Medicine, BeijingChildren’s Hospital, Capital Medical University, Beijing wassupported by an Asia–Pacific Pediatric Association Travel-ling Scholarship provided through the Division of Paedi-atrics & Child Health, The Royal Australasian College ofPhysicians.

References

1. Kelley CF, Mannino DM, Homa DM, Savage-Brown A,Holguin F. Asthma phenotypes, risk factors, and measures ofseverity in a national sample of US children. Pediatrics 2005;115: 726–31.

2. Kurukulaaratchy RJ, Fenn M, Matthews S, Arshad SH.Characterisation of atopic and non-atopic wheeze in 10 yearold children. Thorax 2004; 59: 563–8.

3. Ostergaard PA. Non-IgE-mediated asthma in children. ActaPaediatr Scand 1985; 74: 713–9.

4. American Thoracic Society. Standardization of spirometry,1994 update. Am J Respir Crit Care Med 1995; 152: 1107–36.

5. Polgar G, Promadhat V. Pulmonary function testing inchildren: techniques and standards. Philadelphia: WBSaunders, 1971.

6. Ostergaard PA. A prospective study on non-IgE-mediatedasthma in children. Acta Paediatr Scand 1988; 77: 112–7.

7. Eastham KM, Fall AJ, Mitchell L, Spencer DA. The need tore-define non-cystic fibrosis bronchiectasis in childhood.Thorax 2004; 59: 324–7.

8. Ponsonby AL, Gatenby P, Glasgow N, Mullins R, McDonald T,Hurwitz M. Which clinical subgroups within the spectrum ofchild asthma are attributable to atopy? Chest 2002; 121:135–42.

9. Schwindt CD, Tjoa T, Floro JN, McLaren C, Delfino RJ.Association of atopy to asthma severity and medication use inchildren. J Asthma 2006; 43: 439–46.

10. Humbert M, Durham SR, Ying S, Kimmitt P, Barkans J, AssoufiB, et al IL-4 and IL-5 mRNA and protein in bronchial biopsiesfrom patients with atopic and nonatopic asthma: evidence

C©2007 The Author(s)/Journal Compilation C©2007 Foundation Acta Pædiatrica/Acta Pædiatrica 2007 96, pp. 1088–1094 1089

Effects of HAART in orphaned African children Ble et al

against “intrinsic” asthma being a distinct immunopathologicentity. Am J Respir Crit Care Med 1996; 154: 1497–504.

11. Nja F, Roksund OD, Carlsen KH. Eosinophil cationic protein(ECP) in school children living in a mountainous area ofNorway: a population-based study of ECP as a tool fordiagnosing asthma in children with reference values. Allergy2001; 56: 138–44.

12. Taira M, Tamaoki J, Kondo M, Kawatani K, Nagai A. SerumB12 tryptase level as a marker of allergic airway inflammationin asthma. J Asthma 2002; 39: 315–22.

13. Pumputiene I, Emuzyte R, Dubakiene R, Firantiene R,Tamosiunas V. T cell and eosinophil activation in mild andmoderate atopic and nonatopic children’s asthma in remission.Allergy 2006; 61: 43–8.

Efficacy of highly active antiretroviral therapy in HIV-infected,institutionalized orphaned children in TanzaniaClaudio Ble1, Marco Floridia ([email protected])2, Celine Muhale3, Stephen Motto3, Marina Giuliano2, Andrea Gabbuti1, Lucia Giuman1, Francesco Mazzotta1

1.Department of Infectious Diseases, S.M. Annunziata Hospital, ASL, Florence, Italy2.Department of Drug Evaluation and Research, Istituto Superiore di Sanita, Rome, Italy3.Hope Village Medical Center, Dodoma, Tanzania

CorrespondenceDr. Marco Floridia, Department of Drug Evaluationand Research, Istituto Superiore di Sanita,Viale Regina Elena 299, 00161 Rome, Italy.Tel: +39.06.4990.3228 |Fax: +39.06.4938.7199 |Email: [email protected]

Received11 December 2006; revised 12 March 2007;accepted 13 April 2007.

DOI: 10.1111/j.1651-2227.2007.00352.x

With the increasing access to antiretroviral therapy, thereis growing and consistent evidence that highly active an-tiretroviral therapy (HAART) can induce significant bene-fits in HIV-infected adult patients in resource-limited coun-tries (1–5). Some information is also becoming available onthe effectiveness of HAART in vertically infected children insuch settings.

In the context of the Thailand’s national access to an-tiretroviral programme, HAART induced substantial bene-fits in HIV-infected children, with a mortality rate of 3.7%at 72 weeks and positive changes on CD4 percentage, viralload and nutritional indexes (6). Other studies performed indifferent countries suggested that the outcomes in childrenreceiving treatment in resource-limited settings may com-pare well with those obtained in the developed world (7–9)or in adults receiving HAART in Africa (10).

No data are available on the outcome of HAART in insti-tutionalized children in Africa. In such a setting, it is possiblethat a better adherence to HAART and a good nutritional in-take, together with regular medical visits, can contribute tofurther improve survival and morbidity.

Tanzania is a country with a generalized HIV/AIDS epi-demic, where programmes of HAART administration wererecently introduced, allowing wider access to treatment. Wehere report the clinical and immunological effects of HAARTin a group of orphaned HIV-infected children assisted in aresidential structure between 2002 and 2005 in Tanzania.

Potential conflicts of interest: The authors do not have a commercialor other association that might pose a conflict of interest.

The Hope Village is a residential structure for orphanedchildren with HIV infection, situated in the town ofDodoma, Tanzania. A medical doctor is present on site dailyduring morning hours, and nurse care is available full-time(24 h). Laboratory evaluations including haematology, bio-chemistry and CD4+ count can be performed on site. X-rayevaluations are performed at the Regional Hospital (10-kmdistance). All children entering the structure receive a clin-ical and immunological evaluation for HIV disease and achest radiograph. CD4 counts are determined by flow cytom-etry (FACSCount, Becton Dickinson, San Jose, CA, USA).At that time (2002–2005), antiretroviral treatment wasconsidered in the presence of one or more of the follow-ing conditions: HIV-related life-threatening clinical condi-tions or major AIDS-defining events, chronic or recurrentinfections not responding to common treatment (e.g. dis-seminate herpes infections), and low levels of CD4 (definedat the time of this study as absolute number of CD4 below400/mm3). Treated children received a combination regi-men based on nucleoside reverse transcriptase inhibitors(NRTI) plus non-nucleoside reverse transcriptase inhibitors(NNRTI), protease inhibitors (PI) or both. The choice ofthe regimen was made by the attending physician consid-ering the possible need to administer concomitant anti-TBtherapy (11). Both children who were assigned antiretroviraltreatment and those who received no antiretroviral treat-ment, were followed with clinical and immunological as-sessments every 3–6 months until 12 months of follow-up.Weight was measured with a mechanical scale. Length (be-fore 2 years of age) and height were measured using a mea-suring board and a wall-mounted scale. Children with a CD4


Ble et al Effects of HAART in orphaned African children

percentage <25% and all infants <1 year of age receiveddaily pneumocystis carinii pneumonia (PCP) prophylaxiswith cotrimoxazole in accordance with the WHO recom-mendations (12). Tuberculosis (TB) was assessed by clinicaland radiological criteria, plus sputum analysis in the pres-ence of productive cough. Children who were found to beaffected by TB received a combination of pyrazinamide, iso-niazid and rifampin for 2 months, followed by isoniazid plusrifampin for additional 4 months. Anti-TB drugs were ob-tained through WHO programmes, and antiretroviral drugs(which included both generic drugs and brand drugs, ac-cording to drug availability) were obtained directly from themanufacturers or were provided by the National TanzanianGovernment. Consent to use of the data for the present anal-ysis was given by the responsible persons of the missionarystructure.

Weight and height for age were calculated. The height-for-age and weight-for-age Z-scores (HFA-Z and WFA-Z, re-spectively) were calculated by subtracting the median weightor height of the NCHS reference standards (13) at the child’sage from the child’s weight or height and dividing by thestandard deviation of the reference population at that age.

Categorical data were compared using the � 2-test. CD4cell values, body weight, HFA-Z scores and WFA-Z scoresbetween children receiving or not receiving antiretrovi-ral treatment were compared by Student’s t-test for inde-pendent samples. Baseline was defined as the first day oftreatment for treated children and as day of first visit foruntreated children. Changes at 12 months from baseline inthe same parameters and in body weight were comparedusing t-test for paired samples. Clinical events were clas-sified as major, HIV-related (pneumonia, TB, salmonellosis,cryptococcal meningitis), major, non-HIV-related (malaria),and minor (bronchitis, chickenpox, cutaneous mycoses,otitis, upper respiratory infections, parotitis, molluscum,herpes, impetigo, infestations). Only major events were con-sidered for analysis. The risk of major events during follow-up was assessed in treated and untreated children usingrelative risks (RR) with 95% confidence intervals (CI). Alldata were analysed using the SPSS software, version 13.0(SPSS, Inc., Chicago, USA).

Study population included all the HIV-infected childrenwho were followed in 2002–2005 at the structure (Fig. 1).None of them had previously received antiretroviral treat-ment. Two children, who died with limited follow-upinformation available, were excluded from the analysis: a2-year-old girl with probable leukaemia (55 000 WBC/mm3,hepatosplenomegaly and malnutrition) who died 4 days af-ter entering the structure, and an 11-month-old girl whodeveloped malaria, received quinine, and died a few daysafter, with a diagnosis of sepsis (CD4 count at 9 monthsof age: 1022/mm3). Both infants received no antiretroviraltreatment.

Among the remaining 103 children (61 male, 42 female,age range: 3–127 months), 59 (57%) started antiretroviraltreatment, after a median interval of 56 days from enter-ing the structure. Fifty-six of these children (94.9%) wouldhave been eligible for treatment according to WHO 2006

Figure 1 Population and follow-up.

paediatric guidelines for resource-limited settings (13). Com-pared to children who did not start treatment, they wereolder (p = 0.003), had significantly lower mean CD4+ ab-solute counts (p < 0.001) and percentages (p < 0.001) anda higher rate of major clinical events (TB or pneumonia)at entry (p = 0.045) (Table S1). Both treated and untreatedchildren had moderate to severe malnutrition at entry, as ex-pressed by low values of both HFA-Z and WFA-Z scores.Among treated children, the majority received a three-drug, two-class regimen, mostly represented by zidovudine(ZDV) plus lamivudine (3TC) plus nelfinavir (NFV) (21/59,36%), and by ZDV+3TC+nevirapine (NVP) (19/59, 32%)(Table S1).

During follow-up, 35 children (59.3%) underwent achange in treatment (after a median of 164 days), mostly(24/35, 68.7%) because of adjustments and constraints re-quired by concomitant anti-TB treatment. The other reasonsfor changing treatment were adverse events in six children(4 neutropenia, 11.4%, 2 anaemia, 5.7%), and low CD4 inone (2.6%).

All the children were still followed clinically at 12 months.Paired values (baseline/12 months) of CD4+ absolute countswere available for 27 untreated (61%) and for 45 treated(76%) children. Fourteen untreated children (32%) and 16treated children (27%) had also paired CD4 percentagesavailable for analyses.



Figure 2 Nutritional indexes (HFA and WFA Z-scores) at baseline and 12 months in the treated and untreated children.

Mean changes from baseline in CD4 absolute counts andpercentages at 12 months are reported in Table S2. Both pa-rameters increased significantly in treated children, attaining12-month levels of 660 cells/mm3 and 25.3%, respectively.In untreated children, the CD4 percentage at 12 monthsshowed a slight and non-significant decrease compared tobaseline (−2.9%); the CD4 absolute count, although signif-icantly decreased compared to baseline, still remained high(776/mm3). Among the 27 untreated children with availableCD4 data at 12 months, only 2 (7.4%) became eligible for an-tiretroviral treatment according to WHO 2006 guidelines.

Malnutrition significantly improved: overall, at12 months, children in both groups gained about 1point in both HFA and WFA Z-scores (p < 0.001 forall values), indicating a significant positive effect of thegeneral care provided in reversing the baseline condition ofmalnutrition (Fig. 2).

Treated and untreated children did not differ in occur-rence during follow-up of major events (52.5% vs. 61.4%,respectively, RR for treated children = 0.8; 95% CI : 0.5–1.3,p = 0.372) or of HIV-related events (37.3% vs. 36.4%, re-spectively, RR for treated children = 1.0; 95% CI : 0.6–1.6,p = 0.923). The number of events per child was similar in thetwo groups (0.75 and 0.79 events per child in the untreatedand treated group, respectively). Pneumonia and TB wereresponsible for most of such events (54.5% and 59.5% of theevents in the untreated and treated children, respectively).

We describe the clinical and immunological effects ofHAART among HIV-infected, institutionalized children liv-ing in a resource-poor country. After 1 year of treatment,children with severe malnutrition and declined CD4 valueshad significant increases in both CD4 cell percentages (from10.3 to 25.3%) and absolute count (from 310 to 660/mm3).Such results are consistent with those observed in other co-horts (6–8). Z-score values increased significantly in bothtreated and untreated children, reflecting an important over-all improvement in nutritional status for all the childrenassisted at the structure. Most importantly, no follow-upmortality was observed among the children who entered thestructure, with the exception of two early cases, who werehowever apparently unrelated to HIV disease. As shownby others (2), TB was a very common cause of morbid-ity, and represented the main reason underlying changesin antiretroviral treatment. Overall, respiratory events (TBand pneumonia) were responsible for approximately 60%of major events during follow-up, confirming the high oc-currence of such events in HIV-infected African childrenreceiving HAART (14). Treatment-limiting adverse eventswere rather infrequent, and circumscribed to haematologicaleffects.

Compared to other studies, we also showed that institu-tionalized children who do not meet the criteria for treat-ment can be safely monitored for immunological status withno mortality and no difference in clinical events compared


Ble et al Effects of HAART in orphaned African children

to treated children in the short-term. Importantly, our re-sults suggest that the better survival that we observed, com-pared to that recently reported for orphaned children byNyandiko et al. (15), can be attributed to the particular set-ting of our study, represented by a residential structure wherechildren receive regular general medical care (allowing earlydetection of opportunistic infections and adverse events),adequate nutrition and directly administered antiretroviraltreatment.

Our study has some limitations: these include the rela-tively short duration of follow-up, which may reduce thepossibility to draw conclusions on long-term efficacy. Thisdrawback is, however, common to other published studies.We are also unable to provide viral load information, whichwas collected only since late 2005, but this reflects currenttrends in resource-limited countries, where viral load testingis being gradually introduced in treatment programmes.Some of the children had missing follow-up CD4 measure-ments. This is also not uncommon, even in developed coun-tries, and we believe that a 70% rate of availability of CD4data may be considered satisfactory in this setting. Moreover,this is not likely to affect the overall clinical conclusions, be-cause all the children were still followed for morbidity at1 year.

The use of local criteria for treatment initiation at the in-stitution might represent a further limitation of the study;according to the 2006 WHO guidelines, about 20% of un-treated children but almost all treated children would havenow been eligible for treatment. We therefore consider thata similar treatment response can be expected using currentrecommended criteria. Different regimens were used as first-line treatment, due to constraints represented by drug avail-ability and concomitant anti-TB treatment. However, potentcombinations were always used.

In conclusion, our results provide further evidence on thepossibility to use safely and effectively antiretroviral therapyin HIV-infected children living in resource-limited countries.Such findings support the concept that local and interna-tional initiatives aimed at providing antiretroviral treatmentand care to HIV-infected adults and children have a signifi-cant impact on the natural history of the disease in any partof the world.

ACKNOWLEDGEMENTSWe wish to thank all the people working at the center, sisterM. Rosaria Gargiulo and father Vincenzo Boselli for theircontinuous and dedicated support to all the activities of theHope Village and for their help in the data collection for thiswork. We also thank Tonino Sofia for providing commentsand help in the revision of the final manuscript.

References

1. Coetzee D, Hildebrand K, Boulle A, Maartens G, Louis F,Labatala V, et al. Outcomes after two years of providingantiretroviral treatment in Khayelitsha, South Africa. AIDS2004; 18: 887–95.

2. Pujari SN, Patel AK, Naik E, Patel KK, Dravid A, Patel JK,et al. Effectiveness of generic fixed-dose combinations ofhighly active antiretroviral therapy for treatment of HIVinfection in India. J Acquir Immune Defic Syndr 2004; 37:1566–9.

3. Ivers LC, Kendrick D, Doucette K. Efficacy of antiretroviraltherapy programs in resource-poor settings: a meta-analysis ofthe published literature. Clin Infect Dis 2005; 41: 217–24.

4. Bourgeois A, Laurent C, Mougnutou R, Nkoue N, Lactuock B,Ciaffi L, et al. Field assessment of generic antiretroviral drugs:a prospective cohort study in Cameroon. Antivir Ther 2005;10: 335–41.

5. Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A,Miotti P, et al. Antiretroviral therapy in lower incomecountries (ART-LINC) collaboration; ART cohortcollaboration (ART-CC) groups. Mortality of HIV-1-infectedpatients in the first year of antiretroviral therapy: comparisonbetween low-income and high-income countries. Lancet 2006;367: 817–24.

6. Puthanakit T, Oberdorfer A, Akarathum N, Kanjanavanit S,Wannarit P, Sirisanthana T, et al. Efficacy of highly activeantiretroviral therapy in HIV-infected children participating inThailand’s National Access to Antiretroviral Program. ClinInfect Dis 2005; 41: 100–7.

7. Fassinou P, Elenga N, Rouet F, Laguide R, Kouakoussui KA,Timite M, et al. Highly active antiretroviral therapies amongHIV-1-infected children in Abidjan, Cote d’Ivoire. AIDS 2004;18: 1905–13.

8. Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G,et al. Antiretroviral therapy in a thousand patients with AIDSin Haiti. N Engl J Med 2005; 353: 2325–34.

9. O’brien DP, Sauvageot D, Zachariah R, Humblet P, forMedecins Sans Frontieres. In resource-limited settings goodearly outcomes can be achieved in children using adultfixed-dose combination antiretroviral therapy. AIDS 2006; 20:1955–60.

10. Rouet F, Fassinou P, Inwoley A, Anaky MF, Kouakoussui A,Rouzioux C, et al. for the ANRS 1244/1278 ProgrammeEnfants Yopougon. Long-term survival and immuno-virological response of African HIV-1-infected children tohighly-active antiretroviral therapy regimens. AIDS 2006; 20:2315–19.

11. WHO. Antiretroviral therapy of HIV infection in infants andchildren in resource-limited settings: towards universal access.Recommendations for a public health approach. Geneva,Switzerland: World Health Organization, 2006.

12. UNAIDS/WHO. Provisional WHO/UNAIDS secretariatrecommendations on the use of cotrimoxazole prophylaxis inadults and children living with HIV/AIDS in Africa. Geneva:UNAIDS, 2000. http://data.unaids.org/Publications/IRC-pub04/recommendation en.pdf?preview=true. Accessed May2, 2006.

13. WHO. Management of the child with a serious infection orsevere malnutrition: guidelines at the first referral level indeveloping countries. Geneva, Switzerland: World HealthOrganization, 2000.

14. Kouakoussui A, Fassinou P, Anaky MF, Elenga N, Laguide R,Wemin ML, et al. Respiratory manifestations in HIV-infectedchildren pre- and post-HAART in Abidjan, the Ivory Coast.Paediatr Respir Rev 2004; 5: 311–5.

15. Nyandiko WM, Ayaya S, Nabakwe E, Tenge C, Sidle JE,Yiannoutsos CT, et al. Outcomes of HIV-infected orphanedand non-orphaned children on antiretroviral therapy inwestern Kenya. J Acquir Immune Defic Syndr 2006; 43;418–25.



Supplementary materialThe following supplementary material is available for thisarticle:

Table S1. General baseline characteristics.Table S2. Mean changes from baseline in CD4 cell countsand Z-scores (height for age and weight for age).

This material is available as part of the online article from:

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1651-2227.2007.00352.x(This link will take you to the article abstract).

Please note: Blackwell Publishing are not responsible forthe content or functionality of any supplementary materialssupplied by the authors. Any queries (other than missingmaterial) should be directed to the corresponding authorfor the article.


pulmonary function in non-atopic and atopic childhood asthma

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