[A clinical analysis of 9 cases of pulmonary alveolar proteinosis with secondary infection].

OBJECTIVE: To describe the clinical characteristics of 9 cases of idiopathic pulmonary alveolar proteinosis (iPAP) with secondary infections. METHOD: The clinical and radiological data of 9 patients with iPAP and secondary infections admitted into Peking Union Medical College Hospital from 1st January 1990 to 1st January 2010 were retrospectively analyzed. RESULTS: In that period, there were 97 patients of iPAP were admitted in our hospital. There were 9 patients of iPAP with secondary infections, aged (46.4 ± 14.6) y. There were 5 males and 4 females. Among them, 6 patients were misdiagnosed as interstitial pneumonia and corticosteroids were given to them. When the infection appeared, corticosteroids were still given to 3 patients, and the other 3 patients had stopped corticosteroids for 3 to 15 and a half months. Five patients had accepted mono-lung or whole lung lavage before 1, 2, 9, 14, 24 months. The clinical manifestations were fever (8 cases), cough (9 cases), expectoration (8 cases), hemoptysis (2 cases), chest pain (1 case) and moist rales (1 case). Glass-ground opacities (9 cases) and cavitations (4 case) were the main manifestations of chest radiology. Pleural effusions (1 case) was not common. The locations of infection was limited in chest: 9 cases had pulmonary infection and one case was associated with pleurisy. The infectious pathogens were the acid-fast tubercle bacillus (4 cases), fungus (3 cases, candida albicans, penicillium and aspergillus fumigatus for each one) and nocardia (2 cases, one case was associated with cytomegalovirus infection). FOLLOW-UP: 6 patients were cured, 1 patient was improved and 2 patients were died. CONCLUSIONS: For patients with iPAP, especially when they had been receiving corticosteroids, if they had fever and/or recently exaggerated dyspnea, especially whose chest radiology showed nodules and cavitations, the clinicians should be aware of infections diseases for them. Further specific microbiological studies and sufficient therapy should be obtained as quickly as possible.

Pulmonary histoplasmosis: unusual histopathologic findings.

Four patients with clinical diagnosis of interstitial lung disease (ILD) are presented. In these patients, lung biopsies revealed bronchocentric granulomatosis (BG), pulmonary alveolar proteinosis (PAP), diffuse alveolar damage (DAD), and in one biopsy, the clinical manifestations suggested tuberculous primo-infection with systemic dissemination. Three patients died without diagnosis. In all four cases, specific histological stains found Histoplasma capsulatum. Histoplasmosis may mimic other infectious or non-infectious pulmonary diseases, such as interstitial and granulomatous pulmonary disease. Therefore, the absolute need for identification of the organism by culture or special stains cannot be over-emphasized and may lead to a proper mycological diagnosis. This highlights the importance of differential diagnosis with systemic infectious diseases, especially in areas where deep-seated mycosis are endemic.

Isolation of mycobacteria in patients with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by accumulation of proteinaceous material in the alveoli of affected individuals. Pulmonary infections appear to develop with increased frequency in these patients. The increased rate of infection has been attributed to immunologic aberrations, such as impaired alveolar macrophage function, particularly when uncommon pathogens are involved. Among those pathogens, Nocardia asteroides and Mycobacterium tuberculosis have appeared most often in case reports in the literature. Mycobacterium avium-intracellulare (MAI) has rarely been isolated in these patients. We report an unusually high incidence of MAI isolation from lavage fluid in 8 of 19 consecutive patients who underwent therapeutic lung lavage for relief of symptomatic PAP, and summarize the available literature on isolation of potential respiratory pathogens in PAP.

Pulmonary alveolar proteinosis as a terminal complication in myelodysplastic syndromes: a report of four cases detected on autopsy.

Secondary pulmonary alveolar proteinosis (PAP) is one of the complications of hematologic malignancy and immunosuppressive diseases. We encountered four cases of myelodysplastic syndrome (MDS) associated with PAP detected on autopsy. They consisted of two refractory anemia (RA) and two patients with refractory anemia with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but all of them developed leukemic phase and were resistant to chemotherapy at the time of pulmonary episodes. Of the four MDS patients, two also had pulmonary aspergillosis. Previously, 69 patients with PAP associated with hematologic disorders have been reported, but there have been only seven cases with MDS, including our four patients. Of the 69 reported cases of PAP in hematologic malignancies, 24/63 (38%) informative patients with infection had fungal infections of the lung; 2/7 (29%) MDS cases had fungal infection. We should, therefore, pay careful attention to this possibility in cases of MDS with lung complications, including PAP, especially in patients in the leukemic phase of MDS.

Pulmonary alveolar proteinosis.

Three adult patients, two of whom were HIV-seropositive, presented with a dyspnea of two-to-three-day duration associated with dry cough. High-resolution CT scans of the chest revealed a widespread air-space consolidation with "crazy-paving" pattern in all cases, suggesting a pulmonary alveolar proteinosis (PAP). Bronchoalveolar lavage (BAL) retrieved varying amounts of turbid fluid containing abundant, coarsely granular material that stained positively using periodic acid-Schiff (PAS) and PAS with prior diastase digestion. Pneumocystis carinii (PC) cysts were identified in Gomori methenamine silver-stained BAL sediments obtained from the two HIV-positive patients. By electron microscopy, numerous myelin figures were found in the BAL sediments in all cases, confirming a PAP. Histologic examination of lung tissues obtained by open biopsy confirmed a PAP in two cases, with one case showing, in addition, PC cysts.

Pulmonary alveolar proteinosis secondary to Pneumocystis jiroveci infection in an infant with common variable immunodeficiency.

The authors report an infant with common variable immunodeficiency (CVID) with Pneumocystis pneumonia who developed secondary pulmonary alveolar proteinosis (PAP). This is the youngest infant reported to develop PAP secondary to Pneumocystis infection in an immunocompromised state. He was effectively managed with anti-microbials, frequent lung toilet, optimized mechanical ventilation, and supportive care.

Hereditary pulmonary alveolar proteinosis. Could it be triggered by Mycoplasma pneumoniae pneumonia?

We present a three-year-old girl with respiratory failure due to hereditary pulmonary alveolar proteinosis caused by abnormal alpha chain of the granulocyte-macrophage colony-stimulating factor receptor. Both the patient and an asymptomatic seven-year-old sister were homozygous for the same mutation in CSF2RA. We speculate that the Mycoplasma pneumoniae pneumonia might have triggered the clinical presentation. While a good response to serial partial lung lavage was noticed, the ultimate outcome is uncertain.

Recovery of Mycobacterium avium from cigarettes.

Mycobacterium avium was recovered from tobacco, cigarette paper, and cigarette filters. M. avium could also be recovered from cigarette filters after the cigarettes had been smoked.

Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain.

Surfactant protein D (SP-D) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. Because SP-D specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (NSPs): neutrophil elastase, proteinase-3, and cathepsin G degrade SP-D. All three human NSPs specifically cleaved recombinant rat and natural human SP-D dodecamers in a time- and dose-dependent manner, which was reciprocally dependent on calcium concentration. The NSPs generated similar, relatively stable, disulfide cross-linked immunoreactive fragments of approximately 35 kDa (reduced), and sequencing of a major catheptic fragment definitively localized the major sites of cleavage to a highly conserved subregion of the carbohydrate recognition domain. Cleavage markedly reduced the ability of SP-D to promote bacterial aggregation and to bind to yeast mannan in vitro. Incubation of SP-D with isolated murine neutrophils led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired in their ability to degrade SP-D. Using a mouse model of acute bacterial pneumonia, we observed the accumulation of SP-D at sites of neutrophil infiltration coinciding with the appearance of approximately 35-kDa SP-D fragments in bronchoalveolar lavage fluids. Together, our data suggest that neutrophil-derived serine proteinases cleave SP-D at sites of inflammation with potential deleterious effects on its biological functions.