Asthma natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Philip Marcus, M.D., M.P.H. [3]; Associate Editor(s)-in-Chief: Varun Kumar, M.B.B.S. [4]
Overview
Wheezing may occur early in childhood. But in majority of cases, it may not persist into adulthood unless severe or has predisposition to asthma. Asthma progression during childhood vary with gender and may sometimes regress completely unlike adult onset asthma. Prognosis of asthma in absence of other co- morbidities is generally good with treatment and life expectancy is similar to that of general population. Complications of asthma may include status asthmaticus, respiratory failure, candidiasis and cardiac dysfunction.
Natural History
Asthma in Children
- Many children often develop one or more episodes of wheezing early in life. These episodes are often associated with respiratory viral infection.[1] Tucson Children's Respiratory Study, a longitudinal birth cohort study, demonstrated that the prevalence of wheezing in presence of lower respiratory tract illness was 32%, 17% and 12% at first, second and third year of life, respectively.[2] Respiratory syncytial virus (RSV) followed by parainfluenza virus type 3 are the most common causative agents identified.[3][4][2] At age of 6 years, 20% of children who had previous episodes of lower respiratory illness with wheezing during the first three years of life had no wheezing. 13.7% of children who had wheezing before three years of age continued to have wheezing. 15% of children were reported to have new onset wheezing at 6 years of age. The majority of children with wheeze were associated with transient conditions such as viral illness which were found not to increase the risk of asthma later in life.[5] Lung function values among children with persistent wheezing were not different from those who never wheezed. However, their IgE levels were elevated[2] suggesting allergic/ asthma predisposition. The late-onset wheezing and the persistent wheezing groups had more episodes of wheezing in late childhood and adolescence.[6]
- The Melbourne Asthma Study, a longitudinal community based study (1964-1999), evaluated the natural course of asthma from childhood (7 years of age) into adult life (42 years of age) in patients not optimally treated according to present guidelines. The study demonstrated that the children with few episodes of wheezing associated with respiratory infection had a benign course, with many becoming asymptomatic by adult life. While, those with severe asthma during childhood continued to be symptomatic during adulthood and there was a progressive loss in pulmonary function noted as the patients approached 14 years of age but did not progress in adult life. Loss of lung function was not noted in patients with milder symptoms.[7]
- In another birth cohort study in Dunedin, New Zealand 613 children were followed every 2 years between 3 and 15 years of age and then at 18, 21, and 26 years of age.[8] By 26 years of age, approximately 50% of the cohort had reported wheezing at least once. Bronchodilator response (or a positive methacholine test) and a positive skin test result to mite or cat at 9 years of age, predicted the persistence of asthma at 26 years of age.[9]
- Similar to above mentioned studies, the Childhood Asthma Management Program (CAMP) also reported a decline in pulmonary function with age if asthmatic onset is early on in childhood. Significant correlation between duration of asthma and decline in lung function, greater methacholine responsiveness, more asthma symptoms, and greater use of as-needed albuterol was noted from the baseline data of 1041 children. In addition it also reported that independent of baseline lung function, the airway responsiveness increased after puberty in girls, but decreased after puberty in boys.[10]
Asthma in Adults
Asthma in adults may be of new onset or persistent from childhood. Unlike asthma in children, among adults, asthma is seldom clinically progressive or undergo complete remission. However, rapid rate of decline in lung function may be observed among patients with severe asthma[11][12] or those with new onset asthma. The Copenhagen City Heart Study demonstrated this observation where the decline in lung function was, on average, 39 ml/yr in men and 11 ml/yr in women, respectively, compared with that in non- asthmatic subjects. Among patients with chronic asthma, the rate of lung function decline did not increase compared with that in non- asthmatic subjects.[13] Asthmatics who are smokers have higher rates of decline.[14] Relapse rates among patients with past history of asthma tend to increase with age.[15]
Complications
The complications of asthma can be severe. Some include:
- Acute severe exacerbation may progress to status asthmaticus in which asthma symptoms are refractory to initial bronchodilator therapy. Delayed treatment with systemic corticosteroids in such situations or presence of co-existing conditions such as restrictive lung disease or congestive heart failure increase the risk of death.
- Decreased ability to exercise and take part in other activities
- Lack of sleep due to nighttime symptoms
- Decrease in pulmonary function[11] may be observed with age. This may lead to airway remodeling.[16][17]
- Decline in pulmonary function and air way remodelling may increase the risk for airway obstruction, frequent respiratory infections and may ultimately lead to respiratory failure.
- Cardiac dysfunction may occur secondary to decrease in lung function or due to inflammatory response. Right ventricular diastolic and systolic dysfunction were noted in a study involving 64 children with varying degree of severity.[18] However cardiac complications in asthmatics are usually related to treatment of asthma i.e. use of beta agonists or avoidance of beta blockers among patients with pre- existing cardiac conditions.
- Trouble breathing that requires breathing assistance (ventilator) which may cause complications such as pneumothorax and infections.
- Oral thrush may occur in patients using corticosteroid inhalers.
- Relapse of asthma among patients with past history of asthma tend to increase with age.[15]
- Asthma in pregnancy can cause preterm labor[19], pre-eclampsia[20], intra uterine growth retardation[21] or miscarriage[22]. These complications are attributed to hypoxia.[23]
Prognosis
The prognosis for asthmatics is good; especially for children with mild disease. Among those experiencing wheezing during childhood, majority would be symptom free after a decade.[5] However, if the asthma is severe during childhood, it may persist to adulthood.[7] In a birth cohort study in Dunedin, New Zealand, bronchodilator response (or a positive methacholine test) and a positive skin test result to mite or cat at 9 years of age, predicted the persistence of asthma at 26 years of age.[9] The extent of permanent lung damage in asthmatics is unclear. Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes.[24] Although conclusions from studies are mixed, most studies show that early treatment with glucocorticoids prevents or ameliorates decline in lung function as measured by several parameters.[25] For those who continue to suffer from mild symptoms, corticosteroids can help most to live their lives with few disabilities.
It is estimated that 15 million disability-adjusted life years (DALYs) are lost due to asthma worldwide per year and is similar to that for diabetes, cirrhosis of the liver, or schizophrenia.[26]. Asthma cost the US about $3,300 per person with asthma each year from 2002 to 2007 in medical expenses, missed school and work days, and early deaths[27].
Life expectancy is not generally affected by asthma and is not different from general population. However, elderly patients with asthma often die from other respiratory diseases than individuals in general population.[28][29] The mortality rate for asthma is low, with around 6000 deaths per year in a population of some 10 million patients in the United States. Better control of the condition may help prevent some of these deaths.
Biomarkers
Monitoring eosinophilic markers (exhaled nitric oxide or sputum eosinophils) may reduce exacerbation according to a systematic review<ref name="pmid29858277">Petsky HL, Cates CJ, Kew KM, Chang AB (2018). "Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis". Thorax. doi:10.1136/thoraxjnl-2018-211540. PMID 29858277. </.
References
- ↑ Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston SL; et al. (2007). "Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma". J Allergy Clin Immunol. 119 (5): 1105–10. doi:10.1016/j.jaci.2006.12.669. PMID 17353039.
- ↑ 2.0 2.1 2.2 Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD (2003). "Tucson Children's Respiratory Study: 1980 to present". J Allergy Clin Immunol. 111 (4): 661–75, quiz 676. PMID 12704342.
- ↑ Henderson FW, Clyde WA, Collier AM, Denny FW, Senior RJ, Sheaffer CI; et al. (1979). "The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice". J Pediatr. 95 (2): 183–90. PMID 448557.
- ↑ Denny FW, Clyde WA (1986). "Acute lower respiratory tract infections in nonhospitalized children". J Pediatr. 108 (5 Pt 1): 635–46. PMID 3009769.
- ↑ 5.0 5.1 Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ (1995). "Asthma and wheezing in the first six years of life. The Group Health Medical Associates". N Engl J Med. 332 (3): 133–8. doi:10.1056/NEJM199501193320301. PMID 7800004.
- ↑ Dodge R, Martinez FD, Cline MG, Lebowitz MD, Burrows B (1996). "Early childhood respiratory symptoms and the subsequent diagnosis of asthma". J Allergy Clin Immunol. 98 (1): 48–54. PMID 8765817.
- ↑ 7.0 7.1 Phelan PD, Robertson CF, Olinsky A (2002). "The Melbourne Asthma Study: 1964-1999". J Allergy Clin Immunol. 109 (2): 189–94. PMID 11842286.
- ↑ Jones DT, Sears MR, Holdaway MD, Hewitt CJ, Flannery EM, Herbison GP; et al. (1987). "Childhood asthma in New Zealand". Br J Dis Chest. 81 (4): 332–40. PMID 3449120.
- ↑ 9.0 9.1 Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM; et al. (2003). "A longitudinal, population-based, cohort study of childhood asthma followed to adulthood". N Engl J Med. 349 (15): 1414–22. doi:10.1056/NEJMoa022363. PMID 14534334.
- ↑ Strunk RC, Weiss ST, Yates KP, Tonascia J, Zeiger RS, Szefler SJ; et al. (2006). "Mild to moderate asthma affects lung growth in children and adolescents". J Allergy Clin Immunol. 118 (5): 1040–7. doi:10.1016/j.jaci.2006.07.053. PMID 17088127.
- ↑ 11.0 11.1 Peat JK, Woolcock AJ, Cullen K (1987). "Rate of decline of lung function in subjects with asthma". Eur J Respir Dis. 70 (3): 171–9. PMID 3569449.
- ↑ Kelly WJ, Hudson I, Raven J, Phelan PD, Pain MC, Olinsky A (1988). "Childhood asthma and adult lung function". Am Rev Respir Dis. 138 (1): 26–30. PMID 3059867.
- ↑ Ulrik CS, Lange P (1994). "Decline of lung function in adults with bronchial asthma". Am J Respir Crit Care Med. 150 (3): 629–34. PMID 8087330.
- ↑ Lange P, Parner J, Vestbo J, Schnohr P, Jensen G (1998). "A 15-year follow-up study of ventilatory function in adults with asthma". N Engl J Med. 339 (17): 1194–200. doi:10.1056/NEJM199810223391703. PMID 9780339.
- ↑ 15.0 15.1 Bronnimann S, Burrows B (1986). "A prospective study of the natural history of asthma. Remission and relapse rates". Chest. 90 (4): 480–4. PMID 3757559.
- ↑ Covar RA, Spahn JD, Murphy JR, Szefler SJ, Childhood Asthma Management Program Research Group (2004). "Progression of asthma measured by lung function in the childhood asthma management program". Am J Respir Crit Care Med. 170 (3): 234–41. doi:10.1164/rccm.200308-1174OC. PMID 15028558.
- ↑ Homer RJ, Elias JA (2005). "Airway remodeling in asthma: therapeutic implications of mechanisms". Physiology (Bethesda). 20: 28–35. doi:10.1152/physiol.00035.2004. PMID 15653837.
- ↑ Peng SM, Sun P, Zeng J, Deng XM (2006). "[Cardiac function of children with bronchial asthma]". Zhongguo Dang Dai Er Ke Za Zhi. 8 (5): 388–90. PMID 17052399.
- ↑ Perlow JH, Montgomery D, Morgan MA, Towers CV, Porto M (1992). "Severity of asthma and perinatal outcome". Am J Obstet Gynecol. 167 (4 Pt 1): 963–7. PMID 1415433.
- ↑ Triche EW, Saftlas AF, Belanger K, Leaderer BP, Bracken MB (2004). "Association of asthma diagnosis, severity, symptoms, and treatment with risk of preeclampsia". Obstet Gynecol. 104 (3): 585–93. doi:10.1097/01.AOG.0000136481.05983.91. PMID 15339773.
- ↑ Schatz M, Zeiger RS, Hoffman CP (1990). "Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study Group". Chest. 98 (2): 389–92. PMID 2376171.
- ↑ Breton MC, Beauchesne MF, Lemière C, Rey E, Forget A, Blais L (2009). "Risk of perinatal mortality associated with asthma during pregnancy". Thorax. 64 (2): 101–6. doi:10.1136/thx.2008.102970. PMID 19008298.
- ↑ Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W; et al. (2006). "Spirometry is related to perinatal outcomes in pregnant women with asthma". Am J Obstet Gynecol. 194 (1): 120–6. doi:10.1016/j.ajog.2005.06.028. PMID 16389020.
- ↑ Maddox L, Schwartz DA (2002) The pathophysiology of asthma. Annu Rev Med 53 ():477-98. DOI:10.1146/annurev.med.53.082901.103921 PMID: 11818486
- ↑ Beckett PA, Howarth PH. Pharmacotherapy and airway remodelling in asthma? Thorax. 2003;58(2):163-74. PMID 12554904
- ↑ Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma (GINA) Program (2004). "The global burden of asthma: executive summary of the GINA Dissemination Committee report". Allergy. 59 (5): 469–78. doi:10.1111/j.1398-9995.2004.00526.x. PMID 15080825.
- ↑ Centers for Disease Control and Prevention, Vital Signs, May 2011[1]
- ↑ Bauer BA, Reed CE, Yunginger JW, Wollan PC, Silverstein MD (1997). "Incidence and outcomes of asthma in the elderly. A population-based study in Rochester, Minnesota". Chest. 111 (2): 303–10. PMID 9041973.
- ↑ Silverstein MD, Reed CE, O'Connell EJ, Melton LJ, O'Fallon WM, Yunginger JW (1994). "Long-term survival of a cohort of community residents with asthma". N Engl J Med. 331 (23): 1537–41. doi:10.1056/NEJM199412083312301. PMID 7969322.