Asthma: Venekamp, & Bel, 2013). Asthma prevalence

Asthma: Etiology and Public Health Implications

Introduction

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Asthma is a chronic condition of the respiratory system identified by difficulty breathing, wheezing, chest tightness, and cough, symptoms which are indicative of inflammation due to hyperresponsiveness and/or constriction of the airway (National Asthma Education and Prevention Program, 2007). It is a disease often beginning in childhood and persisting into adulthood. However, there have been several studies showing cases of adult-onset asthma as well as recent trends of increasing incidence of such cases (Nijs, Venekamp, & Bel, 2013).

Asthma is a heterogenous disease, thus making effective management and treatment challenging. About 56 billion dollars were spent in 2007 towards the treatment and management of asthma in the United States (Lang, 2015). Various causes and risk factors have been identified, including mode of delivery, breastfeeding, air pollution, obesity, and more (Salam, et al., 2006; Nijs, Venekamp, & Bel, 2013). Asthma prevalence varies widely across the globe, although there has been an overall net increase in the incidence of asthma in recent years (Subbarao, Mandhane, & Sears, 2009).

Four main asthma subtypes have been identified based on the strength of the inflammatory response, which is in turn influenced by the types of cells present in the airway (Ishmael, 2011; Lang, 2015). The airway microbiome is also thought to play a role in the inflammatory response (Mitchell & O’Byrne, 2016). Current treatments already target these cells as well as the microbiome. Recent research proposes vitamin D as a therapeutic measure for the more severe forms of asthma (M.Brehm, et al., 2010).

 

 

Prevalence and global trends

Asthma affects more than 20 million Americans, adults and children inclusive (Lang, 2015). Global prevalence varies widely and is dependent on a combination of genetic and environmental component factors. For example, the prevalence of asthma in Asian countries is only about 2% to 4% of the population, compared to 15% to 20% in developed countries such as the United States and Canada (Subbarao, Mandhane, & Sears, 2009). Another study recorded higher incidence and prevalence rates for asthma in males compared to females during childhood and the reverse after the occurrence of puberty (Arathimos, Granell, Henderson, Relton, & Tilling, 2017). There has been an overall global increase in asthma prevalence in recent years (Subbarao, Mandhane, & Sears, 2009). Within the United States alone, the Centers for Disease Control and Prevention (CDC) reported a 12.3% increase in prevalence between 2001 and 2009 in a recent Morbidity and Mortality Weekly Report (2011).

Prevalence in different locations varies due to factors such as migration, air pollution, seasonal allergens and infections, and more. Several studies have shown a positive association between migration and the risk of developing asthma, particularly when migration is to more urbanized or more developed regions. One study comparing asthma prevalence among Chinese children showed a lower prevalence among those living in China compared to those who migrated to developed countries (Subbarao, Mandhane, & Sears, 2009). Another study recorded an 11.1% increase in the prevalence of asthma symptoms among migrants for every year lived in Australia compared to their counterparts living in their home countries (Gibson, Henry, Shah, Powell, & Wang, 2003).

 

 

Pathobiology

A.    Inflammatory response in asthma

Four main asthma subtypes have been identified by degree of severity, namely: intermediate asthma, mild persistent asthma, moderate persistent asthma, and severe persistent asthma (Lang, 2015). The degree of severity is thought to be a function of how intense the inflammatory response is during an asthma episode. The respiratory epithelium is essential to mediating the inflammatory response in asthma as it interacts with pollutants, microbes, allergens, and other stimuli. These interactions trigger a cascade that results in the production of cytokines and the attraction and activation of mast cells, basophils, eosinophils, neutrophils, and other cellular and chemical components; these, in turn, act as effectors and either cause structural changes in the lungs, leading to constriction of the airways, or cause an increase in the amount of secretion, thus obstructing airflow (Ishmael, 2011; Durrani, Leung, & Ledford, 2011).

Compared to non-asthmatics, individuals with asthma have increased numbers of these effector cells in their airways, hence the increased inflammation which causes the asthma attack episode. Basophils are not found in the airways of non-asthmatics (Hamid, K.Tulic’, Liu, & Moqbel, 2003). Higher numbers of these cells in the airway lead to a stronger inflammatory response and thus account for the more severe types of asthma (Mitchell & O’Byrne, 2016).

In most asthmatics, the inflammatory response is mediated by eosinophils, basophils, mast cells, and helper T-cells. In some other asthmatics, neutrophils are the mediating cells. Only a very small proportion of asthmatics record no increase in inflammation (Mitchell & O’Byrne, 2016). Eosinophils, basophils, mast cells, and helper T-cells contribute to thickening the basement membrane of the lungs, thus narrowing the airway (Durrani, Leung, & Ledford, 2011). Asthma attack episodes stemming from eosinophil-related causes are better controlled using corticosteroids (Chu & Drazen, 2005). In contrast, neutrophils obstruct the airway by stimulating increased production of secretions such as histamine. Neutrophils have also been implicated in acute-onset asthma types, particularly fatal subtypes and those associated with smoking (National Asthma Education and Prevention Program, 2007). Asthma episodes resulting from neutrophilic effects often do not respond to treatment with corticosteroids (Ishmael, 2011) and novel approaches are needed in this regard.

B.     Influence of the microbiome

Asthma severity is also determined by the microflora present within the lungs. In one study’s comparison between asthmatic individuals and healthy controls, asthmatics were found to have greater numbers of pathogenic bacteria among their lung microflora (Mitchell & O’Byrne, 2016). Another study explored the influence of mode of delivery on respiratory outcomes and found that children born via Caesarean section had a higher risk of exposure to infection and a corresponding increased risk for developing asthma (Salam, et al., 2006). Children with pathogenic bacteria such as Streptococcus pneumoniae and Haemophilus influenzae present in their respiratory tracts at birth have a high risk of developing asthma in childhood (Nijs, Venekamp, & Bel, 2013).

Additionally, a disturbance of microbial balance in the gut due to maternal use of antibiotics or formula feeding in early life has been linked to an increased risk of asthma (Fujimura & Lynch, 2015). One study showed that breastfeeding decreased the risk of asthma before the age of 8 in children whose families had a history of wheezing or asthma (Voort, et al., 2012).

 

 

C.    Childhood onset versus adult onset

Adult-onset asthma is defined as onset of asthma after age 12 and has different causes than asthma beginning in childhood. Both types of asthma have genetic and environmental components; however, the environmental components differ. While childhood-onset asthma is often due to factors such as airway microbiome, viral infections, and maternal smoking (Salam, et al., 2006), adult-onset asthma is often linked to occupational exposures to airway irritants. Other risk factors that contribute to asthma beginning in adulthood include psychological stress, the use of aspirin, and obesity. Adult-onset asthma is often more severe and produces more drastic changes in the airway (Nijs, Venekamp, & Bel, 2013).

 

Asthma management: then and now

The treatment approach for asthma has remained essentially the same for over 100 years. The major aspects of asthma treatment have been medications and control of the environment – specifically limiting exposure to triggers. Corticosteroids have been the most important and most effective therapeutic agents for the long-term management of asthma. They are particularly effective for controlling eosinophil-associated asthma types. Antileukotrienes, also known as leukotriene modifiers, block the actions of airway constrictor molecules released by mast cells.  Anti-IgE treatments reduce the severity of asthma episodes by significantly decreasing IgE amounts in the airway as well as interactions with mast cells and basophils (Chu & Drazen, 2005; National Asthma Education and Prevention Program, 2007).

Current interventions available for the management of asthma include emergency treatments, short-term treatment, and long-term treatments. Emergency treatments involve the use of bronchodilators such as ipratropium bromide and albuterol to quickly relax smooth muscle and relieve the constricted airway. In 2007, the National Asthma Education and Prevention Program recommended a comprehensive care plan for managing asthma by severity within different age groups from birth through adulthood and within the particular situations of exercise, pregnancy, and surgery. For each asthma patient, the care plan must incorporate the following four essential aspects of effective treatment and management (2007):

i.                    Assess and monitor the patient to determine the severity of asthma, the level of control the patient has achieved by current treatment methods, and whether adjustments need to be made to the patient’s treatment plan. 

ii.                  Educate the patient, family, and/or other persons involved in the patient’s care for proper self-management of asthma. This also requires a well-documented plan for steps to take for normal daily activities, such as when the patient is at school or at work, as well as steps to take when the patient is ill or in the case of an emergency.

iii.                Limit the patient’s exposure to precipitating factors such as dust mites, air pollutants, or other things in the environment to which the patient may be sensitive.

iv.                Determine the appropriate and most effective medications for both instant relief or short-term control and long-term management of asthma for the patient.

While the current approaches to asthma control have been largely effective, new therapies are needed and are being researched to aid in the control of asthma subtypes that have been resistant to treatment and to slow down the progression from asthma to more chronic conditions such as sleep apnea and chronic obstructive pulmonary disease (COPD). One study proposes vitamin D as a way to reduce the severity of attacks and records a significant reduction in the need for emergent care. Further research is needed to verify the effectiveness of vitamin D as a treatment for asthma (M.Brehm, et al., 2010).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

Conclusion and recommendations

Asthma is a disease of growing public health concern, especially with increasing travel and migration around the world and the rate of increasing onset in adulthood (Nijs, Venekamp, & Bel, 2013). It is important to continue to seek new treatment and management strategies as well as establish proper care routines such as have been suggested by the National Asthma Education and Prevention Program.

 

 

References
Arathimos, R., Granell, R., Henderson, J., Relton, C. L., & Tilling, K. (2017, April). Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts. PLoS ONE, 12(4), 1-17. doi:https://doi.org/10.1371/journal.pone.0176293
Centers for Disease Control & Prevention. (2011). Vital Signs: Asthma Prevalence, Disease Characteristics, and Self-Management Education — United States, 2001–2009. Morbidity and Mortality Weekly Report. Retrieved from http://www.cdc.gov/mmwr
Chu, E. K., & Drazen, J. M. (2005). Asthma – One Hundred Years of Treatment and Onward. American Journal of Respiratory and Critical Care Medicine, 171(11), 1202–1208. doi:https://doi.org/10.1164/rccm.200502-257OE
Durrani, S. R., Leung, D. Y., & Ledford, D. K. (2011). What effect does asthma treatment have on airway remodeling? Current perspectives. Journal of Allergy and Clinical Immunology, 128(3), 439-448. doi:https://doi.org/10.1016/j.jaci.2011.06.002
Fahy, J. V. (2009). Eosinophilic and Neutrophilic Inflammation in Asthma: Insights from Clinical Studies. Proceedings of the American Thoracic Society, 6(3), 256-259. doi: 10.1513/pats.200808-087RM
Fujimura, K. E., & Lynch, S. V. (2015). Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome. Cell Host & Microbe, 17, 592-602. doi:http://dx.doi.org/10.1016/j.chom.2015.04.007
Gibson, P. G., Henry, R. L., Shah, S., Powell, H., & Wang, H. (2003). Migration to a Western Country Increases Asthma Symptoms But Not Eosinophilic Airway Inflammation. Pediatric Pulmonology, 36, 209-215.
Hamid, Q., K.Tulic’, M., Liu, M. C., & Moqbel, R. (2003). Inflammatory cells in asthma: Mechanisms and implications for therapy. Journal of Allergy and Clinical Immunology, 11(1), S5-S17.
Ishmael, F. T. (2011, November). The Inflammatory Response in the Pathogenesis of Asthma. Journal of the American Osteopathic Association, 111(11), S11-S17.
Lang, D. M. (2015). Severe asthma: Epidemiology, burden of illness, and heterogeneity. Allergy & Asthma Proceedings, 36, 419-424.
M.Brehm, J., BrookeSchuemann, L.Fuhlbrigge, A., W.Hollis, B., C.Strunk, R., S.Zeiger, R., . . . Group, C. A. (2010). Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Journal of Allergy and Clinical Immunology, 126(1), 52-58.
Mäkikyrö, E. M., Jaakkola, M. S., & Jaakkola, J. J. (2017). Subtypes of asthma based on asthma control and severity: a latent class analysis. Respiratory Research, 18(24). doi:http://doi.org/10.1186/s12931-017-0508-y
Mitchell, P. D., & O’Byrne, P. M. (2016). Biologics and the lung: TSLP and other epithelial cell-derived cytokines in asthma. Pharmacology & Therapeutics, 169, 104-112.
National Asthma Education and Prevention Program. (2007). Guidelines for the Diagnosis and Management of Asthma – Expert Panel Report 3. Summary Report. Retrieved December 3, 2017, from https://www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf
Nijs, S. B., Venekamp, L. N., & Bel, E. H. (2013). Adult-onset asthma: is it really different? European Respiratory Review, 22(127), 44-52. doi:10.1183/09059180.00007112
Salam, M. T., Margolis, H. G., Mcconnell, R., Mcgregor, J. A., Avol, E. L., & Gilliland, F. D. (2006). Mode of Delivery Is Associated With Asthma and Allergy Occurrences in Children. Annals of Epidemiology, 16(5), 341-346.
Subbarao, P., Mandhane, P. J., & Sears, M. R. (2009, October). Asthma: epidemiology, etiology and risk factors. CMAJ, 181(9), E181-E190.
Voort, A. S.-v., Jaddoe, V., Valk, R. v., Willemsen, S., Hofman, A., Moll, H., . . . Duijts, L. (2012). Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms. European Respiratory Journal, 39, 81-89. doi:10.1183/09031936.00178110
 

 

 

 

Asthma: Etiology and Public Health Implications

Introduction

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For You For Only $13.90/page!


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Asthma is a chronic condition of the respiratory system identified by difficulty breathing, wheezing, chest tightness, and cough, symptoms which are indicative of inflammation due to hyperresponsiveness and/or constriction of the airway (National Asthma Education and Prevention Program, 2007). It is a disease often beginning in childhood and persisting into adulthood. However, there have been several studies showing cases of adult-onset asthma as well as recent trends of increasing incidence of such cases (Nijs, Venekamp, & Bel, 2013).

Asthma is a heterogenous disease, thus making effective management and treatment challenging. About 56 billion dollars were spent in 2007 towards the treatment and management of asthma in the United States (Lang, 2015). Various causes and risk factors have been identified, including mode of delivery, breastfeeding, air pollution, obesity, and more (Salam, et al., 2006; Nijs, Venekamp, & Bel, 2013). Asthma prevalence varies widely across the globe, although there has been an overall net increase in the incidence of asthma in recent years (Subbarao, Mandhane, & Sears, 2009).

Four main asthma subtypes have been identified based on the strength of the inflammatory response, which is in turn influenced by the types of cells present in the airway (Ishmael, 2011; Lang, 2015). The airway microbiome is also thought to play a role in the inflammatory response (Mitchell & O’Byrne, 2016). Current treatments already target these cells as well as the microbiome. Recent research proposes vitamin D as a therapeutic measure for the more severe forms of asthma (M.Brehm, et al., 2010).

 

 

Prevalence and global trends

Asthma affects more than 20 million Americans, adults and children inclusive (Lang, 2015). Global prevalence varies widely and is dependent on a combination of genetic and environmental component factors. For example, the prevalence of asthma in Asian countries is only about 2% to 4% of the population, compared to 15% to 20% in developed countries such as the United States and Canada (Subbarao, Mandhane, & Sears, 2009). Another study recorded higher incidence and prevalence rates for asthma in males compared to females during childhood and the reverse after the occurrence of puberty (Arathimos, Granell, Henderson, Relton, & Tilling, 2017). There has been an overall global increase in asthma prevalence in recent years (Subbarao, Mandhane, & Sears, 2009). Within the United States alone, the Centers for Disease Control and Prevention (CDC) reported a 12.3% increase in prevalence between 2001 and 2009 in a recent Morbidity and Mortality Weekly Report (2011).

Prevalence in different locations varies due to factors such as migration, air pollution, seasonal allergens and infections, and more. Several studies have shown a positive association between migration and the risk of developing asthma, particularly when migration is to more urbanized or more developed regions. One study comparing asthma prevalence among Chinese children showed a lower prevalence among those living in China compared to those who migrated to developed countries (Subbarao, Mandhane, & Sears, 2009). Another study recorded an 11.1% increase in the prevalence of asthma symptoms among migrants for every year lived in Australia compared to their counterparts living in their home countries (Gibson, Henry, Shah, Powell, & Wang, 2003).

 

 

Pathobiology

A.    Inflammatory response in asthma

Four main asthma subtypes have been identified by degree of severity, namely: intermediate asthma, mild persistent asthma, moderate persistent asthma, and severe persistent asthma (Lang, 2015). The degree of severity is thought to be a function of how intense the inflammatory response is during an asthma episode. The respiratory epithelium is essential to mediating the inflammatory response in asthma as it interacts with pollutants, microbes, allergens, and other stimuli. These interactions trigger a cascade that results in the production of cytokines and the attraction and activation of mast cells, basophils, eosinophils, neutrophils, and other cellular and chemical components; these, in turn, act as effectors and either cause structural changes in the lungs, leading to constriction of the airways, or cause an increase in the amount of secretion, thus obstructing airflow (Ishmael, 2011; Durrani, Leung, & Ledford, 2011).

Compared to non-asthmatics, individuals with asthma have increased numbers of these effector cells in their airways, hence the increased inflammation which causes the asthma attack episode. Basophils are not found in the airways of non-asthmatics (Hamid, K.Tulic’, Liu, & Moqbel, 2003). Higher numbers of these cells in the airway lead to a stronger inflammatory response and thus account for the more severe types of asthma (Mitchell & O’Byrne, 2016).

In most asthmatics, the inflammatory response is mediated by eosinophils, basophils, mast cells, and helper T-cells. In some other asthmatics, neutrophils are the mediating cells. Only a very small proportion of asthmatics record no increase in inflammation (Mitchell & O’Byrne, 2016). Eosinophils, basophils, mast cells, and helper T-cells contribute to thickening the basement membrane of the lungs, thus narrowing the airway (Durrani, Leung, & Ledford, 2011). Asthma attack episodes stemming from eosinophil-related causes are better controlled using corticosteroids (Chu & Drazen, 2005). In contrast, neutrophils obstruct the airway by stimulating increased production of secretions such as histamine. Neutrophils have also been implicated in acute-onset asthma types, particularly fatal subtypes and those associated with smoking (National Asthma Education and Prevention Program, 2007). Asthma episodes resulting from neutrophilic effects often do not respond to treatment with corticosteroids (Ishmael, 2011) and novel approaches are needed in this regard.

B.     Influence of the microbiome

Asthma severity is also determined by the microflora present within the lungs. In one study’s comparison between asthmatic individuals and healthy controls, asthmatics were found to have greater numbers of pathogenic bacteria among their lung microflora (Mitchell & O’Byrne, 2016). Another study explored the influence of mode of delivery on respiratory outcomes and found that children born via Caesarean section had a higher risk of exposure to infection and a corresponding increased risk for developing asthma (Salam, et al., 2006). Children with pathogenic bacteria such as Streptococcus pneumoniae and Haemophilus influenzae present in their respiratory tracts at birth have a high risk of developing asthma in childhood (Nijs, Venekamp, & Bel, 2013).

Additionally, a disturbance of microbial balance in the gut due to maternal use of antibiotics or formula feeding in early life has been linked to an increased risk of asthma (Fujimura & Lynch, 2015). One study showed that breastfeeding decreased the risk of asthma before the age of 8 in children whose families had a history of wheezing or asthma (Voort, et al., 2012).

 

 

C.    Childhood onset versus adult onset

Adult-onset asthma is defined as onset of asthma after age 12 and has different causes than asthma beginning in childhood. Both types of asthma have genetic and environmental components; however, the environmental components differ. While childhood-onset asthma is often due to factors such as airway microbiome, viral infections, and maternal smoking (Salam, et al., 2006), adult-onset asthma is often linked to occupational exposures to airway irritants. Other risk factors that contribute to asthma beginning in adulthood include psychological stress, the use of aspirin, and obesity. Adult-onset asthma is often more severe and produces more drastic changes in the airway (Nijs, Venekamp, & Bel, 2013).

 

Asthma management: then and now

The treatment approach for asthma has remained essentially the same for over 100 years. The major aspects of asthma treatment have been medications and control of the environment – specifically limiting exposure to triggers. Corticosteroids have been the most important and most effective therapeutic agents for the long-term management of asthma. They are particularly effective for controlling eosinophil-associated asthma types. Antileukotrienes, also known as leukotriene modifiers, block the actions of airway constrictor molecules released by mast cells.  Anti-IgE treatments reduce the severity of asthma episodes by significantly decreasing IgE amounts in the airway as well as interactions with mast cells and basophils (Chu & Drazen, 2005; National Asthma Education and Prevention Program, 2007).

Current interventions available for the management of asthma include emergency treatments, short-term treatment, and long-term treatments. Emergency treatments involve the use of bronchodilators such as ipratropium bromide and albuterol to quickly relax smooth muscle and relieve the constricted airway. In 2007, the National Asthma Education and Prevention Program recommended a comprehensive care plan for managing asthma by severity within different age groups from birth through adulthood and within the particular situations of exercise, pregnancy, and surgery. For each asthma patient, the care plan must incorporate the following four essential aspects of effective treatment and management (2007):

i.                    Assess and monitor the patient to determine the severity of asthma, the level of control the patient has achieved by current treatment methods, and whether adjustments need to be made to the patient’s treatment plan. 

ii.                  Educate the patient, family, and/or other persons involved in the patient’s care for proper self-management of asthma. This also requires a well-documented plan for steps to take for normal daily activities, such as when the patient is at school or at work, as well as steps to take when the patient is ill or in the case of an emergency.

iii.                Limit the patient’s exposure to precipitating factors such as dust mites, air pollutants, or other things in the environment to which the patient may be sensitive.

iv.                Determine the appropriate and most effective medications for both instant relief or short-term control and long-term management of asthma for the patient.

While the current approaches to asthma control have been largely effective, new therapies are needed and are being researched to aid in the control of asthma subtypes that have been resistant to treatment and to slow down the progression from asthma to more chronic conditions such as sleep apnea and chronic obstructive pulmonary disease (COPD). One study proposes vitamin D as a way to reduce the severity of attacks and records a significant reduction in the need for emergent care. Further research is needed to verify the effectiveness of vitamin D as a treatment for asthma (M.Brehm, et al., 2010).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

Conclusion and recommendations

Asthma is a disease of growing public health concern, especially with increasing travel and migration around the world and the rate of increasing onset in adulthood (Nijs, Venekamp, & Bel, 2013). It is important to continue to seek new treatment and management strategies as well as establish proper care routines such as have been suggested by the National Asthma Education and Prevention Program.

 

 

References
Arathimos, R., Granell, R., Henderson, J., Relton, C. L., & Tilling, K. (2017, April). Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts. PLoS ONE, 12(4), 1-17. doi:https://doi.org/10.1371/journal.pone.0176293
Centers for Disease Control & Prevention. (2011). Vital Signs: Asthma Prevalence, Disease Characteristics, and Self-Management Education — United States, 2001–2009. Morbidity and Mortality Weekly Report. Retrieved from http://www.cdc.gov/mmwr
Chu, E. K., & Drazen, J. M. (2005). Asthma – One Hundred Years of Treatment and Onward. American Journal of Respiratory and Critical Care Medicine, 171(11), 1202–1208. doi:https://doi.org/10.1164/rccm.200502-257OE
Durrani, S. R., Leung, D. Y., & Ledford, D. K. (2011). What effect does asthma treatment have on airway remodeling? Current perspectives. Journal of Allergy and Clinical Immunology, 128(3), 439-448. doi:https://doi.org/10.1016/j.jaci.2011.06.002
Fahy, J. V. (2009). Eosinophilic and Neutrophilic Inflammation in Asthma: Insights from Clinical Studies. Proceedings of the American Thoracic Society, 6(3), 256-259. doi: 10.1513/pats.200808-087RM
Fujimura, K. E., & Lynch, S. V. (2015). Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome. Cell Host & Microbe, 17, 592-602. doi:http://dx.doi.org/10.1016/j.chom.2015.04.007
Gibson, P. G., Henry, R. L., Shah, S., Powell, H., & Wang, H. (2003). Migration to a Western Country Increases Asthma Symptoms But Not Eosinophilic Airway Inflammation. Pediatric Pulmonology, 36, 209-215.
Hamid, Q., K.Tulic’, M., Liu, M. C., & Moqbel, R. (2003). Inflammatory cells in asthma: Mechanisms and implications for therapy. Journal of Allergy and Clinical Immunology, 11(1), S5-S17.
Ishmael, F. T. (2011, November). The Inflammatory Response in the Pathogenesis of Asthma. Journal of the American Osteopathic Association, 111(11), S11-S17.
Lang, D. M. (2015). Severe asthma: Epidemiology, burden of illness, and heterogeneity. Allergy & Asthma Proceedings, 36, 419-424.
M.Brehm, J., BrookeSchuemann, L.Fuhlbrigge, A., W.Hollis, B., C.Strunk, R., S.Zeiger, R., . . . Group, C. A. (2010). Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Journal of Allergy and Clinical Immunology, 126(1), 52-58.
Mäkikyrö, E. M., Jaakkola, M. S., & Jaakkola, J. J. (2017). Subtypes of asthma based on asthma control and severity: a latent class analysis. Respiratory Research, 18(24). doi:http://doi.org/10.1186/s12931-017-0508-y
Mitchell, P. D., & O’Byrne, P. M. (2016). Biologics and the lung: TSLP and other epithelial cell-derived cytokines in asthma. Pharmacology & Therapeutics, 169, 104-112.
National Asthma Education and Prevention Program. (2007). Guidelines for the Diagnosis and Management of Asthma – Expert Panel Report 3. Summary Report. Retrieved December 3, 2017, from https://www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf
Nijs, S. B., Venekamp, L. N., & Bel, E. H. (2013). Adult-onset asthma: is it really different? European Respiratory Review, 22(127), 44-52. doi:10.1183/09059180.00007112
Salam, M. T., Margolis, H. G., Mcconnell, R., Mcgregor, J. A., Avol, E. L., & Gilliland, F. D. (2006). Mode of Delivery Is Associated With Asthma and Allergy Occurrences in Children. Annals of Epidemiology, 16(5), 341-346.
Subbarao, P., Mandhane, P. J., & Sears, M. R. (2009, October). Asthma: epidemiology, etiology and risk factors. CMAJ, 181(9), E181-E190.
Voort, A. S.-v., Jaddoe, V., Valk, R. v., Willemsen, S., Hofman, A., Moll, H., . . . Duijts, L. (2012). Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms. European Respiratory Journal, 39, 81-89. doi:10.1183/09031936.00178110
 

 

 

 

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