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1. Are Environmental Factors for Atopic Eczema in ISAAC Phase Three due to Reverse Causation?

Author

Aït-Khaled, N., Anderson, H.R., Asher, M.I., Beasley, R., Björkstén, B., Brunekreef, B., Crane, J., Ellwood, P., Flohr, C., Foliaki, S., Forastiere, F., García-Marcos, L., Keil, U., Lai, C.K.W., Mallol, J., Mitchell, E.A., Montefort, S., Odhiambo, J., Pearce, N., Robertson, C.F., Stewart, A.W., Strachan, D., von Mutius, E., Weiland, S.K., Weinmayr, G., Williams, H.C., Wong, G., Clayton, T.O., Ellwood, E., Baena-Cagnani, C.E., Gómez, M., Howitt, M.E., Weyler, J., Pinto-Vargas, R., Petrolera de Salud, Caja, Cunha, A.J. D.A., de Freitas Souza, L., Kuaban, C., Ferguson, A., Rennie, D., Standring, P., Aguilar, P., Amarales, L., Benavides, L.A., Contreras, A., Chen, Y.-Z., Kunii, O., Pan, Q. Li, Zhong, N.-S., Aristizábal, G., Cepeda, A.M., Ordoñez, G.A., Bustos, C., Riikjärv, M.-A., Melaku, K., Sa’aga-Banuve, R., Pekkanen, J., Hypolite, I.E., Novák, Z., Zsigmond, G., Awasthi, S., Bhave, S., Hanumante, N.M., Jain, K.C., Joshi, M.K., Mantri, S.N., Pherwani, A.V., Rego, S., Sabir, M., Salvi, S., Setty, G., Sharma, S.K., Singh, V., Sukumaran, T., Suresh Babu, P.S., Kartasasmita, C.B., Konthen, P., Suprihati, W., Masjedi, M.R., Steriu, A., Koffi, B.N., Odajima, H., al-Momen, J.A., Imanalieva, C., Kudzyte, J., Quah, B.S., Teh, K.H., Baeza-Bacab, M., Barragán-Meijueiro, M., Del-Río-Navarro, B.E., García-Almaráz, R., González-Díaz, S.N., Linares-Zapién, F.J., Merida-Palacio, J.V., Ramírez-Chanona, N., Romero-Tapia, S., Romieu, I., Bouayad, Z., MacKay, R., Moyes, C., Pattemore, P., Onadeko, B.O., Cukier, G., Chiarella, P., Cua-Lim, F., Brêborowicz, A., Solé, D., Sears, M., Aguirre, V., Barba, S., Shah, J., Baratawidjaja, K., Nishima, S., de Bruyne, J., Tuuau-Potoi, N., Lai, C.K., Lee, B.W., El Sony, A., Anderson, R., Rutter, Charlotte E., Silverwood, Richard J., Williams, Hywel C., Ellwood, Philippa, Asher, Innes, Garcia-Marcos, Luis, Strachan, David P., Pearce, Neil, and Langan, Sinéad M.

Published
2019
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2. Are environmental factors for atopic eczema in ISAAC phase three due to reverse causation?

Author

Rutter, Charlotte E., Silverwood, Richard J., Williams, Hywel C., Ellwood, Philippa, Asher, Innes, Garcia-Marcos, Luis, Strachan, David P., Pearce, Neil, Langan, Sinead M., Ait-Khaled, N., Anderson, H. R., Asher, M., I, Beasley, R., Bjorksten, B., Brunekreef, B., Crane, J., Ellwood, P., Flohr, C., Foliaki, S., Forastiere, F., Garcia-Marcos, L., Keil, U., Lai, C. K. W., Mallol, J., Mitchell, E. A., Montefort, S., Odhiambo, J., Pearce, N., Robertson, C. F., Stewart, A. W., Strachan, D., von Mutius, E., Weiland, S. K., Weinmayr, G., Williams, H. C., Wong, G., Clayton, T. O., Ellwood, E., Baena-Cagnani, C. E., Gomez, M., Howitt, M. E., Weyler, Joost J., Pinto-Vargas, R., da Cunha, A. J., de Freitas Souza, L., Kuaban, C., Ferguson, A., Rennie, D., Standring, P., Aguilar, P., Amarales, L., Benavides, L. A., Contreras, A., Chen, Y-Z, Kunii, O., Pan, Q. Li, Zhong, N. S., Aristizabal, G., Cepeda, A. M., Ordonez, G. A., Bustos, C., Riikjarv, M-A, Melaku, K., Sa'aga-Banuve, R., Pekkanen, J., Hypolite, I. E., Novak, Z., Zsigmond, G., Awasthi, S., Bhave, S., Hanumante, N. M., Jain, K. C., Joshi, M. K., Khatav, V. A., Mantri, S. N., Pherwani, A., V, Rego, S., Sabir, M., Salvi, S., Setty, G., Sharma, S. K., Singh, V, Sukumaran, T., Babu, P. S. Suresh, Kartasasmita, C. B., Konthen, P., Suprihati, W., Masjedi, M. R., Steriu, A., Koffi, B. N., Odajima, H., al-Momen, J. A., Imanalieva, C., Kudzyte, J., Quah, B. S., Teh, K. H., Baeza-Bacab, M., Barragan-Meijueiro, M., Del-Rio-Navarro, B. E., Garcia-Almaraz, R., Gonzalez-Diaz, S. N., Linares-Zapien, F. J., Merida-Palacio, J., V, Ramirez-Chanona, N., Romero-Tapia, S., Romieu, I, Bouayad, Z., MacKay, R., Moyes, C., Pattemore, P., Onadeko, B. O., Cukier, G., Chiarella, P., Cua-Lim, F., Breborowicz, A., Sole, D., Sears, M., Aguirre, V, Barba, S., Shah, J., Baratawidjaja, K., Nishima, S., de Bruyne, J., Tuuau-Potoi, N., Lai, C. K., Lee, B. W., El Sony, A., Anderson, R., and ISAAC Phase Three Study Grp

Subjects
Human medicine
Abstract

Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual-and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6-7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37-1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10-2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34-1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21-1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00-1.82 and OR = 0.94, 95% CI = 0.69-1.28, respectively). At ages 13-14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51-1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33-1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84-3.59 and OR = 2.38, 95% CI = 1.52-3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27-1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07-1.82). Most individual-and school-level effects were consistent, tending to exclude reverse causation.

Published
2019

3. Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation?

Author

Silverwood, Richard J., Rutter, Charlotte E., Mitchell, Edwin A., Asher, M. Innes, Garcia-Marcos, Luis, Strachan, David P., Pearce, Neil, Ait-Khaled, N., Anderson, H. R., Asher, M. I., Beasley, R., Bjorksten, B., Brunekreef, B., Crane, J., Ellwood, P., Flohr, C., Foliaki, S., Forastiere, F., Garcia-Marcos, L., Keil, U., Lai, C. K. W., Mallol, J., Mitchell, E. A., Montefort, S., Odhiambo, J., Pearce, N., Robertson, C. F., Stewart, A. W., Strachan, D., von Mutius, E., Weiland, S. K., Weinmayr, G., Williams, H. C., Wong, G., Clayton, T. O., Baena-Cagnani, C. E., Gomez, M., Howitt, M. E., Weyler, Joost J., Pinto-Vargas, R., da Cunha, A. J., de Freitas Souza, L., Kuaban, C., Ferguson, A., Rennie, D., Standring, P., Aguilar, P., Amarales, L., Benavides, L. A., Contreras, A., Chen, Y-Z, Kunii, O., Pan, Li, Zhong, N. S., Aristizabal, G., Cepeda, A. M., Ordonez, G. A., Bustos, C., Riikjarv, M-A, Melaku, K., Sa'aga-Banuve, R., Pekkanen, J., Hypolite, I. E., Novak, Z., Zsigmond, G., Awasthi, S., Bhave, S., Hanumante, N. M., Jain, K. C., Joshi, M. K., Khatav, V. A., Mantri, S. N., Pherwani, A. V., Rego, S., Sabir, M., Salvi, S., Setty, G., Sharma, S. K., Singh, V., Sukumaran, T., Babu, P. S. Suresh, Kartasasmita, C. B., Konthen, P., Suprihati, W., Masjedi, M. R., Steriu, A., Koffi, B. N., Odajima, H., al-Momen, J. A., Imanalieva, C., Kudzyte, J., Quah, B. S., Teh, K. H., Baeza-Bacab, M., Barragan-Meijueiro, M., Del-Rio-Navarro, B. E., Garcia-Almaraz, R., Gonzalez-Diaz, S. N., Linares-Zapien, F. J., Merida-Palacio, J. V., Ramirez-Chanona, N., Romero-Tapia, S., Romieu, I., Bouayad, Z., MacKay, R., Moyes, C., Pattemore, P., Onadeko, B. O., Cukier, G., Chiarella, P., Cua-Lim, F., Breborowicz, A., Lis, G., Camara, R., Chiera, M. L., Lopes dos Santos, J. M., Nunes, C., Pinto, J. Rosado, Vlaski, E., Fuimaono, P., Pisi, V., Goh, D. Y., Zar, H. J., Lee, H. B., Blanco-Quiros, A., Busquets, R. M., Carvajal-Uruena, I., Garcia-Hernandez, G., Gonzalez Diaz, C., Lopez-Silvarrey, A., Morales-Suarez-Varela, M., Perez-Yarza, E. G., Musa, O. A., Al-Rawas, O., Mohammad, S., Mohammad, Y., Tabbah, K., Huang, J. L., Kao, C. C., Trakultivakorn, M., Vichyanond, P., Iosefa, T., Burr, M., Holgado, D., Lapides, M. C., Windom, H. H., Aldrey, O., Sole, D., Sears, M., Aguirre, V., Barba, S., Shah, J., Baratawidjaja, K., Nishima, S., de Bruyne, J., Tuuau-Potoi, N., Lai, C. K., Lee, B. W., El Sony, A., Anderson, R., ISAAC Phase Three Study Grp, ISAAC Int Data Ctr, ISAAC Principal Investigators, and ISAAC Natl Coordinators Not

Subjects
Human medicine
Abstract

Background: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication. Objective: To explore the role of reverse causation in risk factors of asthma symptoms. Methods: We compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels. Results: There were 131 924 children aged 6-7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97-2.16), early life antibiotic use (1.65; 1.58-1.73) and open fire cooking (1.44; 1.26-1.65). In school level analyses, these risk factors again showed increased risks. There were 238 586 adolescents aged 13-14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75-1.86), cooking on an open fire (1.32; 1.22-1.43) and maternal tobacco use (1.23; 1.18-1.27). In school level analyses, these risk factors again showed increased risks. Conclusions & clinical relevance: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation.

Published
2019

4. Are Environmental Factors for Atopic Eczema in ISAAC Phase Three due to Reverse Causation?

Author

Rutter, Charlotte E., Silverwood, Richard J., Williams, Hywel C., Ellwood, Philippa, Asher, Innes, Garcia-Marcos, Luis, Strachan, David P., Pearce, Neil, Langan, Sinéad M., Aït-Khaled, N., Anderson, H.R., Asher, M.I., Beasley, R., Björkstén, B., Brunekreef, B., Crane, J., Ellwood, P., Flohr, C., Foliaki, S., Forastiere, F., García-Marcos, L., Keil, U., Lai, C.K.W., Mallol, J., Mitchell, E.A., Montefort, S., Odhiambo, J., Pearce, N., Robertson, C.F., Stewart, A.W., Strachan, D., von Mutius, E., Weiland, S.K., Weinmayr, G., Williams, H.C., Wong, G., Clayton, T.O., Ellwood, E., Baena-Cagnani, C.E., Gómez, M., Howitt, M.E., Weyler, J., Pinto-Vargas, R., Petrolera de Salud, Caja, Cunha, A.J. D.A., de Freitas Souza, L., Kuaban, C., Ferguson, A., Rennie, D., Standring, P., Aguilar, P., Amarales, L., Benavides, L.A., Contreras, A., Chen, Y.-Z., Kunii, O., Pan, Q. Li, Zhong, N.-S., Aristizábal, G., Cepeda, A.M., Ordoñez, G.A., Bustos, C., Riikjärv, M.-A., Melaku, K., Sa’aga-Banuve, R., Pekkanen, J., Hypolite, I.E., Novák, Z., Zsigmond, G., Awasthi, S., Bhave, S., Hanumante, N.M., Jain, K.C., Joshi, M.K., Mantri, S.N., Pherwani, A.V., Rego, S., Sabir, M., Salvi, S., Setty, G., Sharma, S.K., Singh, V., Sukumaran, T., Suresh Babu, P.S., Kartasasmita, C.B., Konthen, P., Suprihati, W., Masjedi, M.R., Steriu, A., Koffi, B.N., Odajima, H., al-Momen, J.A., Imanalieva, C., Kudzyte, J., Quah, B.S., Teh, K.H., Baeza-Bacab, M., Barragán-Meijueiro, M., Del-Río-Navarro, B.E., García-Almaráz, R., González-Díaz, S.N., Linares-Zapién, F.J., Merida-Palacio, J.V., Ramírez-Chanona, N., Romero-Tapia, S., Romieu, I., Bouayad, Z., MacKay, R., Moyes, C., Pattemore, P., Onadeko, B.O., Cukier, G., Chiarella, P., Cua-Lim, F., Brêborowicz, A., Solé, D., Sears, M., Aguirre, V., Barba, S., Shah, J., Baratawidjaja, K., Nishima, S., de Bruyne, J., Tuuau-Potoi, N., Lai, C.K., Lee, B.W., El Sony, A., and Anderson, R.

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5. Are environmental risk factors for current wheeze in the International Study of Asthma and Allergies in Childhood (ISAAC) phase three due to reverse causation?

Author

Silverwood, Richard J., Rutter, Charlotte E., Mitchell, Edwin A., Asher, M. Innes, Garcia‐Marcos, Luis, Strachan, David P., Pearce, Neil, Aït‐Khaled, N, Anderson, HR, Beasley, R, Björkstén, B, Brunekreef, B, Crane, J, Ellwood, P, Flohr, C, Forastiere, F, Foliaki, S, Keil, U, Lai, CKW, Mallol, J, Robertson, CF, Montefort, S, Odhiambo, J, Shah, J, Stewart, AW, Strachan, D, Mutius, E, Weiland, SK, Weinmayr, G, Wong, G, Clayton, TO, Baena‐Cagnani, CE, Gómez, M, Howitt, ME, Weyler, J, Pinto‐Vargas, R, Cunha, AJ, Freitas Souza, L, Kuaban, C, Ferguson, A, Standring, P, Aguilar, P, Amarales, L, Benavides, LA, Chen, Y‐Z, Kunii, O, Li Pan, Q, Zhong, NS, Aristizábal, G, Cepeda, AM, Ordoñez, GA, Bustos, C, Riikjärv, M‐A, Melaku, K, Sa'aga‐Banuve, R, Pekkanen, J, Hypolite, IE, Novák, Z, Zsigmond, G, Awasthi, S, Bhave, S, Hanumante, NM, Jain, KC, Joshi, MK, Khatav, VA, Mantri, SN, Pherwani, AV, Rego, S, Sabir, M, Salvi, S, Setty, G, Sharma, SK, Singh, V, Sukumaran, T, Suresh Babu, PS, Kartasasmita, CB, Konthen, P, Suprihati, W, Masjedi, MR, teriu, A, Koffi, BN, Odajima, H, al‐Momen, JA, Imanalieva, C, Kudzyte, J, Quah, BS, Teh, KH, Baeza‐Bacab, M, Barragán‐Meijueiro, M, Del‐Río‐Navarro, BE, García‐Almaráz, R, González‐Díaz, SN, Linares‐Zapién, FJ, Merida‐Palacio, JV, Ramírez‐Chanona, N, Romero‐Tapia, S, Romieu, I, Bouayad, Z, MacKay, R, Moyes, C, Pattemore, P, Onadeko, BO, Cukier, G, Chiarella, P, Cua‐Lim, F, Brêborowicz, A, Lis, G, Câmara, R, Chiera, ML, Lopes dos Santos, JM, Nunes, C, Rosado Pinto, J, Vlaski, E, Fuimaono, P, Goh, DY, Zar, HJ, Lee, HB, Blanco‐Quirós, A, Busquets, RM, Carvajal‐Urueña, I, García‐Hernández, G, ópez‐Silvarrey Varela, A, Morales‐Suárez‐Varela, M, Pérez‐Yarza, EG, Musa, OA, Al‐Rawas, O, Mohammad, S, Tabbah, K, Huang, JL, Kao, CC, Trakultivakorn, M, Vichyanond, P, Iosefa, T, Burr, M, Holgado, D, Lapides, MC, Windom, HH, Aldrey, O, Solé, D, Sears, M, Barba, S, Baratawidjaja, K, Nishima, S, Bruyne, J, Tuuau‐Potoi, N, Lai, CK, Lee, BW, El Sony, A, and Anderson, R

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