The relationship between respiratory diseases and Down syndrome

By Shaima AlHosani & Ebtihal Mohsin Saleh

SCHS Nurse Unit

Introduction

Down syndrome is a prevalent genetic condition characterized by cognitive impairment and delayed growth. The condition affects approximately 1 in 700 to 1 in 1000 live births. Respiratory issues pose a significant obstacle for individuals with Down syndrome, who often contend with them regularly. Common causes of mortality among this group encompass pneumonia, lung cancer, and viral infections. Many individuals with Down syndrome exhibit structural and functional abnormalities within their respiratory system, particularly in their airways. These irregularities substantially elevate the likelihood of respiratory ailments within this population. The frequent occurrence of respiratory infections profoundly impacts the health and quality of life of individuals with Down syndrome and their families. The study’s goal is to provide a concise overview of the existing understanding of the correlation between particular anomalies in the respiratory system of people with Down syndrome and the increased occurrence of respiratory disorders. Another objective is to propose topics that require deeper investigation. Gaining insight into the factors contributing to the high occurrence of respiratory disorders is the initial stage in devising strategies to avoid or alleviate these diseases, which are a major cause of illness and death in individuals with Down syndrome.(Geier & Geier, 2020; Clift et al., 2021)

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Down syndrome frequently correlates with common respiratory infections due to anatomical factors and a compromised immune system.

People with congenital heart disease frequently observe similar respiratory issues. Anomalies in the respiratory tract and pulmonary parenchyma contribute significantly to illness and death. Some immune system problems that are common in people with Down syndrome, like weakened T-lymphocytes and bad B-lymphocyte function, may make it easier for people to get respiratory diseases. This includes an increased susceptibility to upper respiratory tract infections and pneumonia. Enlarged tonsils and adenoids in approximately 40% of individuals with Down syndrome lead to chronic upper respiratory tract infections. Sleep apnea syndrome, a leading cause of mortality among adults and teens with Down syndrome, results from upper airway lymphoid tissue buildup and relative macroglossia. Recurrent lower respiratory tract infections, often coupled with aspiration common in individuals with dyspraxia and gastroesophageal reflux, frequently lead to bronchiectasis in adults. Case reports note occurrences of pneumatoceles and pneumothorax in Down syndrome individuals during severe lung infections. Children with Down syndrome also face increased risks of acute lymphoblastic leukemia and transient myeloproliferative disorder, which can bring about pulmonary complications and chronic respiratory symptoms. The prevalence of congenital heart disease in Down syndrome populations further exacerbates pulmonary complications, potentially leading to irreversible pulmonary hypertension. Individuals with Down syndrome and large left-to-right shunts may develop Eisenmenger syndrome. Simulation studies show that large airways tend to collapse during exercise, especially in people with intrinsic lung disease and chronic pulmonary blood flow elevation. This may help explain why people with Down syndrome have trouble with exercise. (Illouz et al., 2021) (Santoro et al., 2021) (Malle et al., 2021)

Respiratory symptoms and complications in individuals with Down syndrome

Compared with the extensive knowledge of the cardiovascular disorders in Down syndrome, relatively little attention has been focused on the respiratory system. This is somewhat surprising since respiratory infection has been recognized as a major cause of morbidity and mortality in individuals with Down syndrome. According to a parental report, young children with Down syndrome have a higher prevalence of coughs and coughs associated with fever than non-Down syndrome children living in the same neighborhood. They are more likely to have recurrent pneumonia and a persistent cough. Respiratory infection manifests in a variety of ways. In a retrospective study of 350 medical records of individuals with Down syndrome, respiratory symptoms were the most common presenting complaint, accounting for 12.5% of the total. Males were more likely to have congenital heart disease and less likely to have an ear infection than females. This association between respiratory disease and congenital heart malformation might reflect the similar lower mean age for death from respiratory disease in those with congenital heart disease (27 days) compared with those without heart disease (54 days), although this was not statistically significant. A variety of structural and functional abnormalities of the respiratory tract were described. Respiratory infection may also lead to progressive airway damage, as in immune deficiency, leading to bronchiectasis. Individuals with Down syndrome have an increased prevalence of specific types of immune defects, and there is an increased frequency of IgA and IgG2 deficiency. There are different groups of IgG based on the different H chains. In people with Down syndrome, fewer lymphocytes expressed either γ2 or α chains. (Leung et al., 2023) (Boschiero et al., 2022) (Satty et al., 2023)

Down syndrome respiratory disease diagnosis and management

We used regular conversations with parents to determine outcome measures and to construct a questionnaire using a Delphi approach, involving respiratory pediatricians and general practitioners. This consisted of a 47-item questionnaire that went through two rounds of questions with an agreement of 70% to reach consensus. This tool worked well to identify children with Down syndrome and was thought to be feasible for this group. This questionnaire demonstrated good reproducibility for respiratory illness during testing in a reliability study. This tool was later used to follow up on children with Down syndrome in an observational study for one year. (Marpole et al., 2024) (Fuijkschot et al., 2023)

The causes of these make children with Down syndrome very susceptible to respiratory infections. These can be in the upper airway, such as sinusitis and tonsillitis, or lower airway infections, such as bronchitis or bronchiolitis. Pneumonia is a more serious infection of the lower respiratory tract and can pose a problem in adults. Opportunistic infections such as tuberculosis or other fungal infections have been shown to occur more frequently in individuals with Down syndrome. (Malle et al., 2021) (Chicoine et al., 2021).

In most cases, children with Down syndrome are less able to fight off infections and have a higher prevalence of upper respiratory tract infections. The severity of these has contributed to additional problems such as enlarged adenoids and hypertrophy of the tonsils, which are very common in children with Down syndrome. Obstructive sleep apnea is also a common problem and can have a significant impact on an individual’s health, behavior, and quality of life. It also increases the chances of a child developing diabetes and other cardiovascular conditions. (Eijsvoogel et al., 2022). (Fitzpatrick et al., 2022).

Future research and potential interventions for respiratory health with Down syndrome

The studies that were mentioned above on immune deficiencies and mucus hypersecretion in Down syndrome respiratory disease point out a number of possible areas where people with Down syndrome could be helped to treat and avoid respiratory conditions. However, there remains a paucity of evidence-based information on which to base concrete intervention strategies, and hence the best treatment and prevention of respiratory disease to improve the quality and life expectancy of individuals with Down syndrome is yet to be determined. Future research should consider specific immunity impairments and increased infection rates compared to the general population. A clinical assessment is needed to find out if there are differences in how bad respiratory conditions are in the general population compared to people with Down syndrome. This will also allow for more research into respiratory conditions in groups of people of different ages and levels of severity. This method will allow the determination of the most prevalent respiratory conditions in the Down syndrome population, permitting the targeting of specific conditions with treatments. Identification of specific respiratory conditions and knowledge of the immune defects related to these conditions will allow for more clearly defined intervention strategies that can be implemented to alleviate or prevent respiratory diseases in Down syndrome. (Dimopoulos et al., 2023) (Manti et al., 2023)

Research into the mechanisms underlying the immune and inflammatory responses in the lungs of individuals with Down syndrome suggests a number of potential targets for therapeutic intervention. Immune deficiencies have been identified in the response of individuals with Down syndrome to infections. A study of children with Down syndrome aged 6–60 months old reported that respiratory infections were more common, with the highest incidence being pneumonia (35%), and 40% of these children experienced recurrent respiratory infections. People say that lower numbers of T lymphocytes in the blood and weaker responses to T lymphocyte function in vitro are to blame for the high infection rates. More research suggests that T lymphocytes may not be making enough interferon-gamma. A lack of these nutrients is made worse by problems with neutrophils’ chemotaxis and phagocytosis, which is what causes a lot of people with Down syndrome to get bacterial pneumonia. It has been suggested that the T-lymphocyte immune deficiency is caused by abnormal dendritic cell responses, specifically their increased production of IL-10 and subsequent inhibition of IL-12 production. This suggests that therapies that change the function of dendritic cells could fix the immune problems seen in people with Down syndrome. Aside from immunological deficiencies, increased mucus production has been reported in the respiratory airways of individuals with Down syndrome, although the cause of this phenomenon and its full implications are unknown. Changing the glycosylation of mucin and increasing the levels of MUC2 and MUC5AC mRNA have been linked to mucus overproduction in the airways. This means that targeting mucin gene transcription or the glycosylation of mucin may be possible to reduce mucus overproduction. (De et al., 2020) (Chicoine et al., 2021).

References:

1. Geier, M. R. & Geier, D. A. (2020). Respiratory conditions in coronavirus disease 2019 (COVID-19): Important considerations regarding novel treatment strategies to reduce mortality. Medical hypotheses. sciencedirect.com
2. Clift, A. K., Coupland, C. A., Keogh, R. H., Hemingway, H., & Hippisley-Cox, J. (2021). COVID-19 mortality risk in Down syndrome: results from a cohort study of 8 million adults. Annals of internal medicine, 174(4), 572-576. acpjournals.org
3. Illouz, T., Biragyn, A., Iulita, M. F., Flores-Aguilar, L., Dierssen, M., De Toma, I., … & Okun, E. (2021). Immune dysregulation and the increased risk of complications and mortality following respiratory tract infections in adults with down syndrome. Frontiers in immunology, 12, 621440. frontiersin.org
4. Santoro, S. L., Chicoine, B., Jasien, J. M., Kim, J. L., Stephens, M., Bulova, P., & Capone, G. (2021). Pneumonia and respiratory infections in Down syndrome: A scoping review of the literature. American Journal of Medical Genetics Part A, 185(1), 286-299. google.com
5. Malle, L., Gao, C., Hur, C., Truong, H. Q., Bouvier, N. M., Percha, B., … & Bogunovic, D. (2021). Individuals with Down syndrome hospitalized with COVID-19 have more severe disease. Genetics in Medicine, 23(3), 576-580. nature.com
6. Leung, C., Su, L., Simões-e-Silva, A. C., Arocha, L. S., de Paiva, K. M., & Haas, P. (2023). Risk for severe illness and death among pediatric patients with down syndrome hospitalized for COVID-19, Brazil. Emerging Infectious Diseases, 29(1), 26. nih.gov
7. Boschiero, M. N., Palamim, C. V. C., Ortega, M. M., & Marson, F. A. L. (2022). Clinical characteristics and comorbidities of COVID-19 in unvaccinated patients with Down syndrome: first year report in Brazil. Human Genetics. springer.com
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SHAIMA ABDALLA ALHOSANI AND Ebtihal Mohsen Saleh

SHAIMA ABDALLA ALHOSANI

• Master’s in Nursing
• Bachelor of Science in Nursing
• Acting as a Head of nurse and Member of the Health and Safety Committee in Sharjah City for Humanitarian Services (SCHS)  2023 – Current
• Acting as a Head of the Health Care Department in Sharjah Education Council 2020-2023
• School nurse and team leader in Sharjah Education Council 2012-2019
• Member of the Youth and Adolescent Health Committee
• Member of executive Business Continuity Committee of the Sharjah Education Council
• Member of the ISO Committee of the Sharjah Education Council
• Member of the National Bullying Committee
• Member of the Child Friendly Schools and Nurseries Committee
• Member of the Evaluation and Follow-up Committee for the Covid virus in schools and nurseries
• Member preparing an initial draft of the draft optional UAE standards “Preventing and Combating Bullying.”
• Member of the Sharjah Occupational Health and Safety Standards Team in the education sector
• Member of the Sharjah Occupational Health and Safety Standards Team in the education sector
• First Line of Defense Ambassadors Award
• Volunteer opportunity to take pride in science offered by the Sharjah Education Council to contribute to the organization of virtual awareness activities and programs for community members
• Volunteering Opportunity Volunteer for the endowment offered by the Endowment Department to contribute to reviving the endowment year among community members
• American Heart Association Basic Life Support for Health Care Professional Course
• Diploma in Professional Trainer Preparation
• Adult Mental Health First Aid course by The Light House
• The ICF Coaching program (74 hrs.) by Leadership Works

 

 

Ebtihal Mohsen Saleh

• Bachelor of Nursing
• Imperial Diabetes Educator Course : diabetic educator
• Ibn-Khaldun private school as a school nurse for 8 months
• Sharjah government as school nurse in Sharjah city for humanitarian services since 1/8/2012 until present dealing with different cases of Students with Special need such as Down syndrome, autism, cerebral palsy and mental retardation and some other with psychological and mental disorders as well as DIABETES and Epilepsy cases
• Provide immunization for different age groups according Ministry of Health schedule such as: STUDENTS (Td, DTap, MMR, Varicella, OPV and Rabies vaccine)
• Work during summer time in clinics such as: Waset and Sharjah health center, hospital such as al Kuwait and Alqasmi, nursery such as al Rahmania nursery and al Shaimaa nursery for 7 years.
• Work during covid crisis in al-riq’a clinic and waset clinic for 6 months
• Work as Coordinator of Nursing Licenses for nurses In Sharjah education council and Sharjah City for Humanitarian Services since 2017 until 2019