Study Population
A total of 94 MPP patients (age range: 3 years 4 months–13 years 7 months) were enrolled
in this study. The cohort was 50% male (n=47). All patients in Group LT and 40 patients
in Group NLT were finally diagnosed with RMPP. There was no significant difference
in gender and age between Groups LT and NLT (P>0.05) (Table1).
Clinical characteristics
The average duration of disease before hospitalization was 17.40±13.33 days and 9.27±3.79 days in Groups LT and NLT, respectively (P<0.001).
In Group LT, most patients resided from all over the country and 12 patients had type I respiratory failure, which suggested patients in this group were severe and difficult
to treat. Mean WBC count, CRP level, and LDH concentration were 11.85±4.61×109/L, 104.96±54.20 mg/L, and 681.00±298.24 IU/L, respectively.
In Group NLT, mean WBC count, CRP level, and LDH concentration were 8.47±2.48×109/L, 30.32±20.64 mg/L, and 330.11±81.37 IU/L, respectively.
A clear statistical difference was observed in inflammatory markers (WBC, CRP, LDH)
between the two groups (P<0.001) (Table 1).
Bronchoscopy Findings
In Group LT, bronchoscopy carried out at the early stage of disease revealed mucus plug (Fig. 1B)
and airway mucous necrosis (Fig.2) in 41 (including plastic bronchitis in 6 patients) and 29 patients, respectively. In the late stage of disease, 13 patients had stenosis and 13 patients had AO.
In Group NLT, three patients had a mucus plug and three patients had mucous necrosis in the early stage of disease. In the late stage of disease, bronchoscopy revealed stenosis and AO in three and two
patients, respectively.
A clear statistical difference was observed in airway damage between the two groups
(P<0.05) (table 1).
Chest Imaging Findings
In Group LT, chest imaging at the early stage of disease revealed consolidation with
high density (2/3-1 pulmonary lobe in 4 patients; ≥1 lobe in 46 patients) in 50 patients and pleural effusion in 34 patients. Additionally, chest imaging revealed pulmonary embolism in 8 patients
between 11 and 29 days of disease and necrotizing pneumonia (NP) in 28 patients between
14 and 60 days of disease (Fig. 3).
In Group NLT, chest imaging revealed consolidation with high density (<1/2 pulmonary
lobe in 4 patients, 1/2–2/3 lobe in 24 patients, and 2/3–1 lobe in 11 patients) in 39 patients and bronchiolitis in 5 patients. Only two patients
also had a small amount of pleural effusion.
A clear statistical difference was observed in lung damage between the two groups
(P<0.05) (Table 1).
MP Loads by PCR
MP Loads in Paired Throat Swab and BALF Collected at the Same Time Point
In Group LT, throat swabs were performed in 20 patients 22–45 days after disease;
15 patients were MP-positive (including one patient with 105 copies/mL in 45 days) and 5 patients were MP-negative. Additionally, MP loads in throat swabs were lower than those in BALF. All BALF samples were MP-positive.
In Group NLT, throat swabs were performed in 10 RMPP patients 18–22 days after disease;
3 patients were MP-positive and 7 patients were MP-negative. Five BALF samples were
MP-positive.
These results suggest that patients in Group LT had long-term persistent upper airway
infection and MP was cleared from the upper airway before the lower airway (Table 2).
Maximum MP Loads in BALF
MP loads in BALF were classified into three groups as follows: high bacterial loads
(≥107 copies/mL), moderate bacterial loads (106 copies/mL), and low bacterial loads (<106 copies/mL).
In Group LT, high, moderate, and low MP loads were found in 44 (88%, 44/50), 4 (8%,
4/50), and 2 (4%, 2/50) patients, respectively. In Group NLT, high, moderate, and
low MP loads were found in 2 (5%, 2/44), 5 (11%, 5/44), and 37 (84%, 37/44) patients, respectively. Mean MP loads in BALF were 107.46±0.93 and 104.86±0.93 in Groups LT and NLT, respectively (P<0.001), which suggest MP loads in BALF are associated with the duration of MP infection.
Duration of MP Infection in BALF
In Group LT, MP DNA gradually declined over time in most patients. However, in some
patients, MP copy numbers initially increased and then declined. MP was detected by
PCR within 31–40 days, 41–50 days, 51–60 days, and 61–90 days after disease onset
in 17, 19, 9, and 4 patients, respectively. Cases 1–4 (2 NP patients and 2 AO patients)
had detectable MP loads 61–90 days after disease onset. Moreover, 120 days after disease
onset, MP was detected by PCR in an NP patient (Case 5, 5.98×103 copies/mL).
In Group NLT, 17 patients received more than two treatments of BLT and became MP-negative
by PCR within 30 days of the disease. The remaining 27 patients received BLT once
and were MP-positive by PCR.
These results demonstrate persistent long-term infection in the lower airway of patients
in Group LT.
MP Loads in Peripheral Blood
MP PCR was performed in 20 RMPP patients in Group LT within 7 days of disease. MP
was detected in only one patient with severe RMPP (Case 6, 3.34×103 copies/mL), which suggested a rare MP-associated bloodstream infection. This patient
had type I respiratory failure and a pulmonary embolism.
MP Culture in Long-term MP Infection
In Group LT, MP culture was performed in 15 patients whose MP loads were >105 copies/mL within 31-60 days after disease onset. Twelve of 15 patients were found
to be MP-positive.
Treatment and Clinical Outcomes
All patients were treated with macrolides and BLT and followed up for at least 3 months. Four non-RMPP patients in Group NLT were not treated by glucocorticoid.
In Group LT, moxifloxacin and doxycycline were also added to the treatment course in 14 patients
and 2 patients, respectively. Azithromycin, which has anti-inflammatory effects, was
administered for 3–6 months in 23 patients. Twenty-one patients whose CRP levels were
>100 mg/L received high-dose methylprednisolone therapy (10–30 mg/kg/d for 3 days); after 3 months, chest imaging findings were normal
in only 7 patients. These seven patients had started corticosteroid treatment 7–9
days into the disease course. In Group LT, chest imaging after 3 months of treatment
revealed incomplete absorption of pulmonary lesions in 33 patients, including 13 AO
patients.
In Group NLT, chest imaging after 3 months of treatment revealed incomplete absorption of pulmonary
consolidation in seven patients, including two AO patients.
No obvious side effects were observed in any patients. Furthermore, there were no
deaths in our study.
Taken together, these results indicate MP infection was difficult to clear, and absorption
of lung lesions was very slow, especially in Group LT.