High fever and multi-nodular lung consolidations after whole lung lavage in a patient with pulmonary alveolar proteinosis

A puzzle in this case was high body temperature after whole lung lavage. Persistent high fever, high percentage of neutrophils in blood test, and multiple lung consolidations in bilateral lower fields made it hard to exclude the possibility of secondary bacterial/ fungal infection. In addition, patients with PAP are susceptible to secondary/opportunistic infections due to impaired functions of macrophages and neutrophil (Punatar et al. 2012). However, the initial diagnosis of secondary pulmonary infection was not supported eventually evidenced by as follows: (i) Subsequent culture results from samples of lavage fluid, blood or sputum were negative. (ii) The clinical manifestations were improved after therapies like liquid limitation, glucocorticoid administration and diuretic treatment. In addition, pulmonary edema-induced consolidations are often absorbed completely 72 hour later after effective treatment (Gluecker et al. 1999), which is consistent with our case. (iii) Compared with CRP, PCT is a relatively specifical marker of infection such as respiratory infection or sepsis. A relatively high level of PCT above 2.0 ng/mL has a highly positive predictive value for sepsis or severe sepsis (BalcI et al. 2003). In the present patient, serum PCT was only slightly elevated (0.71 ng/mL) at the time point of high fever. Since other conditions like operative stress may also result in a transitory increase in PCT level (Meisner et al. 1998), the relatively elevated PCT in the present case might represent an acute stress situation of whole lung lavage. Therefore, the diagnosis of lavage fluid-induced pulmonary edema was finally established. Since the high fever can not be explained by secondary lung infection after lung lavage, it is possible that the secondary sterile inflammation and subsequent large absorption of lavage fluid may ascribe to the high body temperature in the current patient.

Not like cardiogenic pulmonary edema, the manifestations of lavage-induced pulmonary edema in CT scan in the current patient display asymmery focal consolidations in posterior segments of bilateral lower fields. Compared to other segments, liquids are relatively hard to be drained completely at basal segments of lower lobes after whole lung lavage. Similar to the current case, focal consolidations in CT scan are also observed in near-drowning patients as a significant feature of pulmonary edema (Gregorakos et al. 2009). Mechanically, residual lavage fluids in the lung lead to local hypoxia, which causes subsequent permeability edema resulting from the releases of inflammatory cytokines and the dmages of capillary and alveolus in corresponding lung fields as observed in Stage 3 of near drowning pulmonary edema (Gluecker et al. 1999). For this case, the rapid improvements in clinical and radiological manifestations might be associated with the fast absorption of residual lavaged fluids from the lung into circulation after liquid limitation and diuretic treatment.

As described in previous studies (Silva et al. 2014; Luisetti et al. 2010; Rebelo et al. 2012), a manual percussion of the alveoli with several cycles of manual ventilation using a continuous positive airway pressure (CPAP) valve with 5 ~ 10 mmHg pressure limit may enhance the removal of the accumulated material. However, we did not perform a percussion of the alveoli in the current case, which might ascribe to the formation of pulmonary edema.

Although the final diagnosis was lavage fluid-induced pulmonary edema (Figure 2), it should be differentiated from other clinical conditions such as organizing pneumonia, alveolar damage, and mechanical oedema. The multi-nodular lung consolidations were occurred just one day after lung lavage and almost completely absorbed in three days later. In addition, the patient had no relapse during the period of hospitalization and the six months of follow-up after discharge; However, organising pneumonia has a subacute presentation between 1 and 12 weeks, remains some residual changes like fibrotic non-specific interstitial pneumonia in CT scan after effective treatments, and is easy to relapse (Beardsley and Rassl 2013). The features including a rapid onset, a quickly complete absorption of multi-nodular lung consolidations, and no relapse in the current case suggested that it was not likely organising pneumonia. As the saline was instilled into the lung under gravitational effect from a height not exceeding 40 centimeters above mid-axillar line according to the procedure described previously (Silva et al. 2014), it might not cause the alveolar damage or mechanical oedema by the lavage itself. In addition, ventilator associated lung injury occurs often in the conditions of high inspiratory transpulmonary pressure (barotrauma), alveolar overdistention (volutrauma), repetitive opening and closing of collapsed alveoli (atelectrauma) and biotrauma (Sutherasan et al. 2014). However, the parameters of mechanical ventilator in the case were at a low level with a fraction of inspiratory oxygenof 40%, a pressure support of 12 cmH₂O, and a tidal volume of 8 ml/kg. Thus, it might be impossible to cause ventilator associated lung injury in the case.