Optimization strategy for the early timing of bronchoalveolar lavage treatment for children with severe mycoplasma pneumoniae pneumonia

Object

The subjects included 684 children with MPP admitted to the Department of Pediatrics of the First Affiliated Hospital of Xinxiang Medical University from January 2019 to December 2021, among whom 244 patients completed TBAL treatment. The inclusion criteria for non-SMPP(NSMPP) were as follows: Meet the diagnostic criteria for pneumonia [11]; MP-DNA positive by multiple polymerase chain reaction (PCR) of BAL fluid and indications for BAL include radiologically confirmed large pulmonary lesions, consolidation, atelectasis and poor response to macrolide treatment. The parents and relatives need to consent to the bronchoalveolar lavage and signed the informed consent form. The exclusion criteria were as follows: the attending physician considered that the cause of the disease was other pathogens; patients with chronic respiratory diseases (e.g., bronchiectasis, asthma, congenital heart disease, pulmonary hypertension, active pulmonary tuberculosis), congenital inherited metabolic diseases, malignant tumors; patients with cardiac arrest, organ transplantation, or surgery; patients with a hospital-acquired infection, immunodeficiency, or use of immunosuppressive drugs; incomplete BAL treatment; and incomplete information. The diagnostic criteria for SMPP were as follows [12]: NSMPP patients had at least three of the following five items: dyspnea and chest retraction (less than 1-year-old: RR ≥ 50 beats/min, HR ≥ 150 beats/min; 1–5 years old: RR ≥ 40 beats/min, HR ≥ 140 beats/min; over 5 years old: RR ≥ 30 beats/min, HR ≥ 120 beats/min); Oxygenation index < 250 mmHg; Hypercapnia; Altered consciousness; Elevated blood urea nitrogen; and Hypotension requiring fluid resuscitation. The Ethics Committee of our hospital approved this study protocol (EC-022-044) and waived the requirement for informed consent due to retrospective nature of the study.

Study design

Grouping: All patients were divided into SMPP and NSMPP groups [12] according to the severity of the disease. In addition, according to the fiberoptic bronchoscopy (FOB) time after admission, the patients were divided into early TBAL group (receiving TBAL within 24 h of admission) and late TBAL group(receiving TBAL after 24 h of admission). Demographic characteristics(e.g., sex, age, length of hospital stay, time of onset before ICU admission), clinical manifestations(e.g., fever, cough, wheezing), laboratory tests(e.g., MP-DNA, procalcitonin (PCT), interleukin-6 (IL-6), immunoglobulin, lymphocyte subsets), computed tomography (CT) score, sequential organ failure assessment (SOFA) score, Acute Physiology and Chronic Health Assessment (APACHE) II scores before BAL, and bronchitis score (BS) by re-analyzed of FOB were collected.

FOB and BAL

Lavage solution was instilled 3–5 times at 1 ml/kg/time. A solution of 0.9% sodium chloride was utilized for the BAL procedure and heated to a temperature of 37℃. The saline solution was recovered under a negative pressure of 6.65–13.3 kPa (50–100 mmHg); the volume of BAL fluid recovery was 40% and more. The combination of Midazolam(0.1-0.3 mg/kg per time, 1ml:5 mg, Jiangsu Enhua Pharmaceutical Co., LTD., H20143222) and propofol (2.5 mg/kg, 20ml:200 mg, Fresenius Kabi AB, J20130013H20143222) was utilized in all procedures to achieve moderate sedation. Additionally, lidocaine hydrochloride(1-2ml per time, 5ml:100 mg, Shanghai Zhaohui Pharmaceutical Co., LTD., H31021071) was applied at the nasal and alveolar lavage site to minimize cough reflex and respiratory spasm. Satisfactory sedation was achieved after 1–2 doses of the Midazolam and propofol combination, and it lasted for 20 min until the completion of the procedure. In addition to measuring the heart rate, respiration, and blood oxygen saturation using the ECG monitor, sufficient oxygen supply was also ensured.

Bronchitis scoring

The bronchoscopy video data were reviewed and scored by several experienced bronchoscopists unaware of the patient’s clinical history. The scoring sites were in the trachea, right main bronchus, right upper lobe, right bronchus intermedius, right middle lobe, right lower lobe, left main bronchus, left upper lobe (including lingula), and left lower lobe, totaling nine sites. Each site was scored for the following six bronchoscopic visual features: amount and color of secretions, presence or absence of mucosal edema, elevation, erythema, and pallor. The volume score is a measure of the amount of secretion in the bronchial lumen. It ranges from 1 to 6, with higher scores indicating a greater presence of secretions. The scoring system for secretions is as follows:Score 1: No secretions are observed in any sites. Score 2: Bubbly secretions are present in less than 5 sites, but do not fill the bronchial lumen.Score 3: Bubbly or viscous secretions are present in more than 5 sites, and fill less than 1/3 of the bronchial lumen.Score 4: Viscous secretions are present in any site, and fill more than 1/3 of the bronchial lumen, or less than 1/2 of the sites have viscous secretions.Score 5: More than 1/2 of the sites have viscous secretions, or less than 1/2 of the sites have bronchial lumens blocked by secretions.Score 6: More than half of the bronchial lumens are blocked by secretions. The color of the secretions was scored according to the BronkoTest® sputum color chart, with a color score ranging from 0 to 8. The first round of scoring was conducted as follows: mucosal edema, eminence, erythema, and pallor features were scored from 0 to 2 according to severity level (0, none; 1, mild; 2, moderate to severe). The second round correction scoring was conducted as follows: For each site’s mucosal appearance, a composite score from 0 to 3 was given based on the number of affected sites (0, none; 1, 50% of the nine sites received 1 point; 3, > 50% of the nine sites scored > 2 points) [13]. For cases with large differences in scores between the two physicians, the case was re-scored by both physicians simultaneously to ensure the reliability and consistency of the bronchitis score results.

CT scoring

CT scoring [14] was first assigned according to the extent of ground-glass opacity changes involving lung lobes (each of the five lung lobes could have a maximum score of 5), with scores defined as follows: 0 for no involvement; 1 for  75% involvement. Three types of CT manifestations (i.e., ground-glass opacity, paving stone sign, and consolidation) were assigned different weights. If a lung lobe showed a paving stone sign, the baseline CT score was increased by 1; if it showed consolidation (with or without a paving stone sign), the baseline CT score was increased by 2. The total CT score was the sum of the scores for each of the five lung lobes, ranging from 0 to 35.

Statistical analysis

Statistical analysis was conducted using GraphPad Prism 8.0. Continuous variables with normal distribution are expressed as the mean ± standard deviation, and those with a non-normal distribution are defined as the median (interquartile range). An unpaired t-test, nonparametric t-test, or Mann–Whitney U test was used to compare the differences between the two groups. One-way analysis of variance was used to compare multiple continuous variables. Categorical variables were expressed as percentages and compared between two groups by chi-square test, continuity correction test, or Fisher’s exact test. Kaplan–Meier analysis was used to evaluate the effect of lavage times and time on hospitalization time, and the log-rank test was used to compare the results. Multivariate logistic regression analysis of laboratory tests, BS, CT score, SOFA score and APACHE II score was used to screen independent risk factors for SMPP, and a nomogram model was established to predict SMPP risk using R 4.2.2 software. The bootstrap method was used to perform internal validation of the model, and a calibration curve and receiver operator characteristic (ROC) curve were drawn to evaluate the accuracy and robustness of the model. The Hosmer–Lemeshow test was used to assess the model’s goodness of fit. P-values < 0.05 indicated statistical significance.