This study described the incidence and related factors of pneumothorax in patients with PCP and their prognosis. In addition, we analyzed survival outcomes in patients with PCP and acute respiratory failure. The development of pneumothorax in PCP was not associated with increased 28-day mortality; however, patients with pneumothorax had difficulty and prolonged MV weaning. Among several factors, CMV co-infection was associated with the development of pneumothorax.
There are several complications associated with PCP . Among them, pneumothorax occurs with prevalence of 5–20% , and is known to occur frequently in patients with conditions leading to increased intrathoracic pressure, including airway disease and interstitial lung disease . Pneumothorax is also a common complication during ventilator treatment, with a reported incidence of 4–15% [13–15]. Patients with acute respiratory distress syndrome are more vulnerable to the occurrence of pneumothorax, with further higher risks in patients with underlying lung disease, than those who do not have this syndrome . In our study population of patients with acute respiratory failure requiring MV care, which is a risk factor for pneumothorax , the incidence of pneumothorax was 18.5% (22/119), which is high. Furthermore, underlying lung diseases, including airway disease and interstitial lung disease, showed relation to increased occurrence of pneumothorax in the univariate analysis, in accordance with a previous report .
We found that there were no significant differences in MV parameters between the patients with- and without pneumothorax. Some studies showed that ventilator parameters, such as peak airway pressure, tidal volume, and PEEP, had no correlation with increased risk of pneumothorax [19–21], although earlier studies had reported relevance . Miller et al reported that protective lung strategies had an effect on decreasing barotrauma . We had managed patients with tidal volumes of 6–7 mg/kg and peak pressures lower than 35 cmH2O, according to the lung protective strategy . We showed that respiratory mechanics did not significantly affect the development of pneumothorax in patients with PCP when this lung protective strategy was applied. Furthermore, in one study, Boussarsar et al. said that barotrauma during MV care was more strongly associated with underlying lung conditions and compliance than with MV parameters .
In immunocompromised patients, PCP commonly presents with co-infection of other pathogens, especially CMV . The reports on effect and outcome of CMV co-infection with PCP are controversial [27, 28], although there are several researches stating that concurrent infection of CMV is related to increased mortality and poor prognosis [29, 30]. Our study showed that CMV antigenemia was not associated with a high mortality rate; however, patients with CMV antigenemia were significantly associated with increased occurrence of pneumothorax. In our study populations, the effect of CMV reactivation on PCP prognosis is meaningful because the seropositivity of CMV in Koreans was reported as high as 94.1% . Cook et al. suggested that CMV reactivation could cause abnormal cytokine/chemokine expression, resulting in pulmonary fibrosis in an animal model . In one prior research on histopathological findings in 12 deceased patients with PCP, three had evidence of CMV co-infection, and two of them presenting with pulmonary fibrosis . Furthermore, structural changes in lung parenchyma, including fibrosis, is one of proposed mechanisms of pneumothorax and increases vulnerability to the occurrence of pneumothorax .
Occurrence of PCP in patients without HIV has poorer progress and higher mortality than that in patients with HIV . In our study, the in-hospital mortality rate was high at 71.4%, will only 28 patients (23.5%) achieving MV weaning. Pneumothorax in patients with PCP with- or without HIV was difficult to treat and had a worse prognosis than pneumothorax from other etiologies [9, 17, 36]. However, in our study, the development of pneumothorax was not associated with increased mortality. In a previous study, acute respiratory failure requiring invasive MV was found to be a risk factor for increased mortality; therefore, the effect of pneumothorax was likely to be lessened because all patients enrolled our study already had respiratory failure . However, we found that development of pneumothorax in patients with PCP who required invasive MV procedures made weaning difficult.
Our study had several limitations. First, this study was retrospectively conducted at a single center. However, we enrolled a large number of patients with PCP and respiratory failure without HIV requiring invasive MV procedures. Furthermore, since all enrolled patients were applied MV, the bias of applying MV could be reduced. Second, we did not acquire microbiological findings from patient samples for diagnosis of PCP but only diagnosed via P. jirovecii PCR assays. However, the sensitivity and specificity of this assay for detecting P. jirovecii were comparable to those of microscopic staining . Furthermore, we included only patients who were treated for PCP with typical symptoms of pneumonia and characteristic radiological findings. Third, in patients discharged to long-term outpatient care after survival, it was not possible to investigate final success of MV weaning.
Nevertheless, our study also had some strengths. We analyzed a large number of patients with PCP and acute respiratory failure, and found related factor of pneumothorax. ICU clinicians might predict that patients with PCP and CMV antigenemia have increased risk of pneumothorax. Additionally, development of pneumothorax in patients with PCP could be a predictive factor of delayed MV weaning and poor final outcome. These results could be helpful to the real clinical field ICU clinician. However, further prospective studies are needed to validate our findings.
The results of this study suggest that pneumothorax development in patients with PCP and acute respiratory failure was not associated with increased 28-day mortality. However, patients with PCP who develop pneumothorax might have difficulty and delayed weaning from MV. Concomitant CMV antigenemia could be a predictive factor for pneumothorax occurrence. Therefore, clinicians need to closely observe the occurrence of pneumothorax in patient with PCP and CMV antigenemia and should anticipate that MV weaning may be difficult in such patients.