Diagnosing pediatric pneumonia in field studies can be challenging owing to the development and presentation of the condition, as well as varied case definitions and surveillance approaches across studies. To address these issues, investigators from the Household Air Pollution Intervention Network (HAPIN) trial (ClinicalTrials.gov Identifier: NCT02944682), in conjunction with external pneumonia experts, formed a working group to provide recommendations for study design and implementation ahead of the upcoming intervention trial. The results of the working group discussions were published in Lancet Respiratory Medicine.
According to researchers, the definition and classification of both severe and nonsevere pneumonia is a “well-recognized challenge,” because no existing classification system is considered a gold standard. The risk for misclassification exists due to the use of different case definitions across studies. Currently, no single, universally accepted definition of pneumonia exists.
This challenge can be met through the use of standardized diagnostic algorithms, such as the World Health Organization’s (WHO) pneumonia case definition — commonly used in low- and middle-income settings outside of hospitals. This classification, revised in 2014, divides pneumonia in children aged 2 to 59 months into 2 categories, which have been lauded as “straightforward, generalizable, and easy to implement in resource-poor settings.”
Based on the results of an extensive literature review, which focused on various diagnostic and imaging challenges for pneumonia, the working group was able to provide a recommended case definition and ancillary testing methods that can be used to diagnose severe pneumonia in field trials.
First, the working group suggested that investigators assess respiratory symptoms. If cough or difficulty breathing is observed, the assessment should be continued for clinical signs, such as fever and tachycardia. Because these symptoms have low specificity and present variably, the working group recommended that the presence of tachypnea, chest indrawing, or other signs of severe respiratory distress be determined. Pneumonia should be defined as “severe” if a child presents with either 1 of the general danger signs described by the WHO or hypoxemia.
The working group also recommended that pneumonia outcome studies use a standardized case definition, as proposed by the WHO, instead of a definition that relies on physician diagnosis. They recommended that tachypnea be defined as a respiratory rate using either the integrated management of childhood illnesses definition (≥60 breaths/min for children aged <2 months, ≥50 breaths/min for children aged 2-11 months, and ≥40 breaths/min for children aged 12-59 months) or age-specific upper limit of normal thresholds for the reference population.
Additionally, the working group recommended that general danger signs, as defined by the WHO, be used to identify severe cases of pneumonia and to increase the specificity of a pneumonia diagnosis. One potential limitation of using the WHO definition is, they noted, that these signs may be too nonspecific. Researchers can mitigate this limitation by using more specific signs of severe respiratory distress and by adding hypoxemia and moderate to severe malnutrition to the list of danger signs. The working group also recommended testing for malaria and other coinfections “if relevant to the local context.”
Finally, the working group recommended that a case definition of pneumonia be based on the acute presentation of respiratory signs and symptoms (<14 days before disease presentation) and ancillary testing via either pulse oximetry or chest imaging. The group also recommended that hypoxemia be defined as a peripheral capillary oxygen saturation measurement of <93%; this measurement should be further refined for children at higher altitudes.
For the upcoming HAPIN trial, investigators plan to use the following: a combination of respiratory symptoms and signs (cough or difficulty breathing, tachypnea, and presence of chest indrawing), the presence of a general danger sign to indicate severity (severe pneumonia defined by the WHO), and ancillary testing with pulse oximetry and chest imaging.
In addition to these diagnostic criteria, HAPIN investigators will identify children with potential cases of severe pneumonia at select health facilities using HAPIN-standardized equipment. Home visits will provide researchers with an opportunity to identify and capture missed pneumonia cases and to reinforce behavioral messaging about seeking care.
“As study objectives differ based on the type of intervention and study setting, the pneumonia case definition and surveillance strategy should be carefully considered before implementing pneumonia outcome studies,” the researchers concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Goodman D, Crocker ME, Parvaiz F, et al; for the HAPIN Investigators. Challenges in the diagnosis of pediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group [published online October 4, 2019]. Lancet Respir Med. doi:10.1016/S2213-2600(19)31249-8