Asthma Phenotypes: the Evolution from Clinical to Molecular Approaches

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2012 May 8

PMID 22561835

Citations 884

Authors

Sally E Wenzel

Affiliations

Soon will be listed here.

Abstract

Although asthma has been considered as a single disease for years, recent studies have increasingly focused on its heterogeneity. The characterization of this heterogeneity has promoted the concept that asthma consists of multiple phenotypes or consistent groupings of characteristics. Asthma phenotypes were initially focused on combinations of clinical characteristics, but they are now evolving to link biology to phenotype, often through a statistically based process. Ongoing studies of large-scale, molecularly and genetically focused and extensively clinically characterized cohorts of asthma should enhance our ability to molecularly understand these phenotypes and lead to more targeted and personalized approaches to asthma therapy.

Citing Articles

Role of environmental pollutants-induced ferroptosis in pulmonary diseases.

Yang L, Qiao Y, Huang Z, Chen Y, Zhang E, Liu Z Front Med (Lausanne). 2025; 12:1542275.

PMID: 40066170 PMC: 11891068. DOI: 10.3389/fmed.2025.1542275.

Beta-Hydroxybutyrate Inhibits Bronchial Smooth Muscle Contraction.

Fastiggi V, Mank M, Caporizzo M, Poynter M bioRxiv. 2025; .

PMID: 40060651 PMC: 11888348. DOI: 10.1101/2025.02.24.639075.

Integration of functional genomics and statistical fine-mapping systematically characterizes adult-onset and childhood-onset asthma genetic associations.

Zhong X, Mitchell R, Billstrand C, Thompson E, Sakabe N, Aneas I medRxiv. 2025; .

PMID: 40034789 PMC: 11875274. DOI: 10.1101/2025.02.11.25322088.

The molecular and metabolic landscape of ferroptosis in respiratory diseases: Pharmacological aspects.

Wu T, Ji M, Li T, Luo L J Pharm Anal. 2025; 15(1):101050.

PMID: 40034685 PMC: 11873008. DOI: 10.1016/j.jpha.2024.101050.

Beta-Hydroxybutyrate Attenuates Bronchial Smooth Muscle Pro-Inflammatory Cytokine Production.

Fastiggi V, Mank M, Poynter M bioRxiv. 2025; .

PMID: 40027689 PMC: 11870512. DOI: 10.1101/2025.02.19.639048.

References

Komakula S, Khatri S, Mermis J, Savill S, Haque S, Rojas M . Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics. Respir Res. 2007; 8:32. PMC: 1855924. DOI: 10.1186/1465-9921-8-32. View

Helenius I, Tikkanen H, Sarna S, Haahtela T . Asthma and increased bronchial responsiveness in elite athletes: atopy and sport event as risk factors. J Allergy Clin Immunol. 1998; 101(5):646-52. DOI: 10.1016/S0091-6749(98)70173-3. View

Yu M, Eckart M, Morgan A, Mukai K, Butte A, Tsai M . Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma. J Clin Invest. 2011; 121(8):3133-43. PMC: 3148724. DOI: 10.1172/JCI43598. View

Borish L, Nelson H, Lanz M, Claussen L, Whitmore J, Agosti J . Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med. 1999; 160(6):1816-23. DOI: 10.1164/ajrccm.160.6.9808146. View

Slager R, Hawkins G, Ampleford E, Bowden A, Stevens L, Morton M . IL-4 receptor α polymorphisms are predictors of a pharmacogenetic response to a novel IL-4/IL-13 antagonist. J Allergy Clin Immunol. 2010; 126(4):875-8. PMC: 3772526. DOI: 10.1016/j.jaci.2010.08.001. View

Dougherty R, Sidhu S, Raman K, Solon M, Solberg O, Caughey G . Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol. 2010; 125(5):1046-1053.e8. PMC: 2918406. DOI: 10.1016/j.jaci.2010.03.003. View

Peters-Golden M, Swern A, Bird S, Hustad C, Grant E, Edelman J . Influence of body mass index on the response to asthma controller agents. Eur Respir J. 2006; 27(3):495-503. DOI: 10.1183/09031936.06.00077205. View

Murdock B, Shreiner A, McDonald R, Osterholzer J, White E, Toews G . Coevolution of TH1, TH2, and TH17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia. Infect Immun. 2010; 79(1):125-35. PMC: 3019910. DOI: 10.1128/IAI.00508-10. View

Lajoie S, Lewkowich I, Suzuki Y, Clark J, Sproles A, Dienger K . Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol. 2010; 11(10):928-35. PMC: 2943538. DOI: 10.1038/ni.1926. View

10.

Dahlen S, Malmstrom K, Nizankowska E, Dahlen B, Kuna P, Kowalski M . Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med. 2002; 165(1):9-14. DOI: 10.1164/ajrccm.165.1.2010080. View

11.

Spanevello A, Confalonieri M, Sulotto F, Romano F, Balzano G, Migliori G . Induced sputum cellularity. Reference values and distribution in normal volunteers. Am J Respir Crit Care Med. 2000; 162(3 Pt 1):1172-4. DOI: 10.1164/ajrccm.162.3.9908057. View

12.

Siroux V, Basagana X, Boudier A, Pin I, Garcia-Aymerich J, Vesin A . Identifying adult asthma phenotypes using a clustering approach. Eur Respir J. 2011; 38(2):310-7. DOI: 10.1183/09031936.00120810. View

13.

Hallstrand T, Moody M, Wurfel M, Schwartz L, Henderson Jr W, Aitken M . Inflammatory basis of exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2005; 172(6):679-86. PMC: 2041799. DOI: 10.1164/rccm.200412-1667OC. View

14.

Saha S, Berry M, Parker D, Siddiqui S, Morgan A, May R . Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol. 2008; 121(3):685-91. PMC: 3992379. DOI: 10.1016/j.jaci.2008.01.005. View

15.

Hanania N, Alpan O, Hamilos D, Condemi J, Reyes-Rivera I, Zhu J . Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011; 154(9):573-82. DOI: 10.7326/0003-4819-154-9-201105030-00002. View

16.

Black J, Roth M . Intrinsic asthma: is it intrinsic to the smooth muscle?. Clin Exp Allergy. 2009; 39(7):962-5. DOI: 10.1111/j.1365-2222.2009.03270.x. View

17.

Szefler S, Phillips B, Martinez F, Chinchilli V, Lemanske R, Strunk R . Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005; 115(2):233-42. DOI: 10.1016/j.jaci.2004.11.014. View

18.

Wenzel S, Wilbraham D, Fuller R, Burmeister Getz E, Longphre M . Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet. 2007; 370(9596):1422-31. DOI: 10.1016/S0140-6736(07)61600-6. View

19.

Gibson P, Simpson J, Hankin R, Powell H, Henry R . Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma. Thorax. 2003; 58(2):116-21. PMC: 1746565. DOI: 10.1136/thorax.58.2.116. View

20.

Bachert C, Wagenmann M, Hauser U, Rudack C . IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol. 1997; 99(6 Pt 1):837-42. DOI: 10.1016/s0091-6749(97)80019-x. View