Clinical Context

Pneumonia is one of the most common reasons for hospital admission among young children, and Streptococcus pneumoniae remains a leading cause of pneumonia in this age group. But a study by Wasserman and colleagues that appeared in the June 2021 issue of Emerging Infectious Diseases confirms that there has been a strong decline in the overall health effect of S pneumoniae since the introduction of the pneumococcal conjugate vaccine (PCV) among children.^[1]

The PCV was first applied broadly among US children in 2000, with an initial 7-valent vaccine. This form of PCV was eventually replaced by a 13-valent vaccine. The Wasserman study finds that PCV resulted in approximately 282,000 fewer cases of invasive pneumococcal disease among children younger than 5 years during the past 2 decades. That includes about 16,000 cases of meningitis and 172,000 cases of bacteremia. Overall, the case rate of invasive pneumococcal disease among young children declined 91% between 1997 and 2019, with annual rates of pneumonia hospitalization declining between 66% and 79%. PCV was not just efficacious for invasive infection. The authors estimate that PCV resulted in 97 million fewer outpatient visits for otitis media among children younger than 5 years.

PCV is valuable for many reasons, one of which is the fact that previous observational research has demonstrated a higher risk for chronic respiratory illness associated with pneumonia among young children. These studies usually included all children, including children with chronic disease, which would also increase the risk for chronic respiratory illness. The current study focuses on the risk for respiratory illness among healthy young children hospitalized for pneumonia.

Study Synopsis and Perspective

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7000 individuals.

"Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage," write Rotem Lapidot, MD, from Boston University, Massachusetts, and colleagues. Previous research has linked pneumonia to subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the effect of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine, the researchers identified 1343 infants who had CAP in the first 2 years of life and 6715 controls, using a large electronic health records data set (Optum EHR data set) for the period from January 2011 through June 2018.^[2]

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the patients with CAP and controls.

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for patients with CAP vs 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 vs 1.9 per 100 patient-years (relative rate, 3.2) and 1.0 vs 0.2 per 100 patient-years (relative rate, 6.3) for the patients with CAP and controls, respectively.

The distribution of the etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the patients with CAP had only 1 qualifying hospitalization for CAP before 2 years of age, and the mean age at first hospitalization was 8.9 months. "Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred" and were highest for children hospitalized at close to 2 years of age, the researchers noted.

"Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease," the researchers wrote in their discussion of the findings.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they note. "Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae," they conclude.

The study was supported by Pfizer. Lead author Dr Lapidot and several coauthors disclosed financial support from Pfizer, and several coauthors are Pfizer employees.

Respiratory Med. 2022;191:106671.

Clinical Implications

• A previous study finds that PCV resulted in approximately 282,000 fewer cases of invasive pneumococcal disease among children younger than 5 years during the past 2 decades. Overall, the case rate of invasive pneumococcal disease among young children declined 91% from 1997 to 2019, with annual rates of pneumonia hospitalization declining between 66% and 79%. PCV was also estimated to eliminate 97 million outpatient visits for otitis media among children younger than 5 years.
• The current study of healthy children found that both viral and bacterial CAP were risk factors for subsequent chronic respiratory illness among young children. The greatest risk was attributed to CAP occurring between 1 and 2 years of age.
• Outline implications for the healthcare team: The healthcare team should do what it can to prevent CAP among young children. There could be a benefit for their long-term pulmonary health with these interventions.

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