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This study was carried out at the research laboratory of the Hospital for Children and Adolescents, University of Helsinki, Finland, during the years 1994 to 1999. I wish to express my sincere gratitude to the heads of the Hospital for Children and Adolescents and the Hospital for Children and Adolescents, University of Helsinki, Professor Jaakko Perheentupa, Docent Krister Holmberg, and Professor Martti Siimes, for providing excellent facilities and a supportive research atmosphere for research.

I am most grateful to my two supervisors, Professor Vuokko Kinnula, for introducing me to the world of science, and for her unselfish help and guidance through the years, and Professor Kari Raivio, for teaching me scientific reasoning and for the support and encouragement throughout the study.

Docents Matti Nuutinen and Heikki Repo are gratefully acknowledged for their valuable criticism of the manuscript of this thesis. I also wish to thank Heikki Repo and Professor Matti Klockars for being members of my thesis follow-up committee.

I wish to thank Carol Norris for revising the language of the thesis.

I wish to acknowledge my collaborators, Dr. Y.-S. Ho, the people in the research groups of Professor James D. Crapo, Docent Kaija Linnainmaa, and Vuokko Kinnula, especially Essi Lakari, for pleasant cooperation and valuable help during these years.

I am deeply indebted to Sari Lindén and Ritva Löfman for teaching me the basics of laboratory practice, as well as their expert technical assistance during the study. I also owe special thanks to Sinikka Latunen. I wish to thank the head, Professor Erkki Savilahti, and the personnel of the research laboratory for aid and a warm atmosphere for this work.

I wish to address special thanks to all members of our "Radical" research group. Our senior colleagues Kristiina Aalto and Risto Lapatto deserve thanks for valuable help and advice. The friendship of my fellow workers Terhi Ahola, Henrikka Aito, Tiina Asikainen, Anna-Liisa Levonen, Nina Linder, Eeva Martelin, and Mika Saksela are warmly acknowledged. I also wish to thank the other colleagues of mine at the Hospital for Children and Adolescents. The friendly atmosphere in the lab filled with humor has been important to help me through the sometimes hard and frustrating times.

I owe big hugs to all my friends. I am grateful to them for sharing enjoyment and for keeping me touch with life outside the medical and scientific field.

To my parents Maire and Uoti Pietarinen I express my deepest gratitude for their love, support, and encouragement during all of my life. I also owe warm thanks to my parents-in-law, Anja and Pentti Runtti.

Finally, my loving thanks are due to my husband Kimmo for his unfailing love and support, and our wonderful children Juho and his brand-new brother, who have brought so much fun and love to our life. They all keep me remined what is really important in this life.

This study was financially supported by the M.D./Ph.D. program of the University of Helsinki and also by grants from The Finnish Medical Society Duodecim, The Finnish Anti-Tuberculosis Association Foundation, and The Finnish Lung Health Association.

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