Incidence and clinical outcomes of pneumonia in persons with down syndrome in the United States

Janoff, Edward N.; Tseng, Hung Fu; Nguyen, Jennifer; Alfred, Tamuno; Vietri, Jeffrey; McDaniel, Angee; Chilson, Erica; Yan, Qi; Malhotra, Deepa; Istúriz, Raúl; Levin, Myron J.

doi:10.1016/j.vaccine.2023.05.063

Cited by 3 publications

(5 citation statements)

References 26 publications

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“…Another recent retrospective study evaluated the incidence of all-cause pneumonia in subjects with DS, resulting in a higher probability of hospitalization and intensive care compared to those without DS. The mortality figure one year after the first pneumonia was also higher, with 5.7% versus 2.4% [8].…”

Section: Discussionmentioning

confidence: 89%

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Cytomegalovirus Pneumonia in a Patient with Down Syndrome

Perrotta,

Piscopiello,

Rizzo

et al. 2024

Medicina

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Down syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and they represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, when causing interstitial pneumonia, associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient with DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation, and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

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Section: Discussionmentioning

confidence: 89%

“…Subjects with DS have a higher incidence of pneumonia than do people without DS, often requiring hospitalization and intensive care. Frequent comorbidities associated with DS, such as heart disease and neurological disease in adulthood, only partially influence the effect of DS on pneumonia [8].…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Pneumonia in a Patient with Down Syndrome

Perrotta,

Piscopiello,

Rizzo

et al. 2024

Medicina

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“…Excessive genes due to trisomy 21 are associated with impaired regulation of redox state and a resultant increase in oxidative stress, subsequently affecting the development of multiple organs [26] . Such changes also contribute to premature senescence and increased oxidative stress in thymus and other lymphoid organs, worsening progressively with age [26,27] . As a result, in DS patients, impaired T cell immunity gets worse with age, often manifested as a decline in antibody titers generated by childhood vaccinations: in infants or young DS children, DS patients generally exhibit normal lymphocyte count and reveal decent responses to infant vaccines, but such responses progressively get worse with age in some DS patients [27,28] .…”

Section: Down Syndrome (Trisomy 21)mentioning

confidence: 99%

“…Such changes also contribute to premature senescence and increased oxidative stress in thymus and other lymphoid organs, worsening progressively with age [26,27] . As a result, in DS patients, impaired T cell immunity gets worse with age, often manifested as a decline in antibody titers generated by childhood vaccinations: in infants or young DS children, DS patients generally exhibit normal lymphocyte count and reveal decent responses to infant vaccines, but such responses progressively get worse with age in some DS patients [27,28] . ikewise, cognitive functions may decline with age in DS patients, indicating their need for more supportive measures for oxidative stress [14] .…”

Section: Down Syndrome (Trisomy 21)mentioning

confidence: 99%

Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms

Jyonouchi

2023

J Transl Genet Genom

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Autism spectrum disorder (ASD) is a behaviorally defined syndrome affected by multiple genetic and environmental factors. A wide variety of risk factors for ASD have been identified and many of these affect immune functions. This may not be surprising, since the immune system and the nervous system share common signaling mechanisms and affect each other as a part of the neuroimmune network. The ever-expanding scope of inborn errors of immunity (IEIs) has revealed multiple pathogenic gene variants that manifest overlapping clinical features of common neuropsychiatric diseases, including ASD. These IEIs often cause dysregulated immune activation and resultant chronic inflammation affecting multiple organs. Some IEIs also cause changes in morphogenesis and plasticity of the central nervous system. Such patients often present with a puzzling array of clinical features and some of them may be diagnosed with ASD or other neuropsychiatric conditions. The progress of our understanding of disease mechanisms for IEIs at the molecular levels has led to gene-specific treatment measures in some diseases. In addition, some ASD patients are found to have laboratory findings of neuroinflammation that resemble those seen in IEI patients. This may pave the way for applying specific treatment measures used for IEI patients in such ASD patients. This review focuses on describing IEIs that have overlapping features of ASD. Emphasis is also on IEIs that can be treated by targeting identified disease mechanisms. Such information may be helpful for clinicians who are considering genetic/metabolic workup in ASD patients.

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“… 6 , 7 , 8 In a recent study, the incidence of all‐cause pneumonia was increased five‐fold in persons with DS compared to those without DS. 9 Unfortunately, the specific mechanisms underpinning the severity and lethality of infectious lung disease for persons with DS are largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome

Colvin,

Elliott,

Goodman

et al. 2023

FASEB BioAdvances

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ObjectivesWe sought to investigate whether the Dp16 mouse model of Down syndrome (DS) is more susceptible to severe and lethal respiratory tract infection by Streptococcus pneumoniae.Study DesignWe infected controls and Dp16 mice with Streptococcus pneumoniae and measured survival rates. We compared cytokine production by primary lung cell cultures exposed to Streptococcus pneumoniae. We examined lung protein expression for interferon signaling related pathways. We characterized the histopathology and quantified the extent of bronchus‐associated lymphoid tissue. Finally, we examined mouse tissues for the presence of oligomeric tau protein.ResultsWe found that the Dp16 mouse model of DS displayed significantly higher susceptibility to lethal respiratory infection with Streptococcus pneumoniae compared to control mice. Lung cells cultured from Dp16 mice displayed unique secreted cytokine profiles compared to control mice. The Dp16 mouse lungs were characterized by profound lobar pneumonia with massive diffuse consolidation involving nearly the entire lobe. Marked red hepatization was noted, and Dp16 mice lungs contained numerous bronchus‐associated lymphoid tissues that were highly follicularized. Compared to uninfected mice, both control mice and Dp16 mice infected with Streptococcus pneumoniae showed evidence of oligomeric tau aggregates.ConclusionsIncreased susceptibility to severe respiratory tract infection with Streptococcus pneumoniae in Dp16 mice closely phenocopies infection in individuals with DS. The increase does not appear to be linked to overexpression of mouse interferon genes syntenic to human chromosome 21.

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Incidence and clinical outcomes of pneumonia in persons with down syndrome in the United States

Cited by 3 publications

References 26 publications

Cytomegalovirus Pneumonia in a Patient with Down Syndrome

Cytomegalovirus Pneumonia in a Patient with Down Syndrome

Inborn errors of immunity present with neuropsychiatric symptoms overlapping with autistic behavioral symptoms

Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome

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