Optical Biopsies Using Probe-Based Confocal Laser Endomicroscopy for Autoimmune Pulmonary Alveolar Proteinosis.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

The impact of lung ultrasound assessment during a whole lung lavage: A paediatric case of pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.

Response to inhaled granulocyte-macrophage colony-stimulating factor in patient with mild-to-moderate autoimmune pulmonary alveolar proteinosis-24 months of follow-up.

INTRODUCTION: Autoimmune pulmonary alveolar proteinosis (aPAP) is a disease caused by IgG antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). Whole lung lavage (WLL) allows to remove the lipo-proteinaceous material accumulated by the poor clearance of alveolar surfactant. However, it is a complex technique that is not exempt from complications, and in some cases, the patients are refractory, requiring the performance of several WLLs spaced apart in time. MATERIALS AND METHODS: We present the clinical, functional, and radiological evolution after 24 months of follow-up of a patient diagnosis of aPAP refractory to WLL, with performed three therapeutic WLLs spaced 16 and 36 months and serious potentially fatal complications in the last one. RESULTS AND DISSCUSION: After 24 months, no adverse effects have appeared and the great clinical, functional and radiological response is maintained. The patient has been successfully treated with inhaled recombinant human GM-CSF sargramostim.

Autoimmune Pulmonary Alveolar Proteinosis during the Treatment of Idiopathic Inflammatory Myopathy.

Approximately 50% of idiopathic inflammatory myopathies (IIMs) are associated with interstitial lung disease (ILD). Typically, IIM-ILD manifests as nonspecific interstitial pneumonia. We herein report a rare case of a 78-year-old man with autoimmune pulmonary alveolar proteinosis (PAP) that developed during IIM treatment. The diagnosis of autoimmune PAP was based on detecting anti-granulocyte-macrophage colony-stimulating factor antibodies. We postulated that PAP may have been induced by IIM treatment with prednisolone. Our case suggests that the possibility of autoimmune PAP should be considered in patients with lung lesions during the clinical course of IIM.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

Autoimmune Pulmonary Alveolar Proteinosis with Suspected Exacerbation after Osimertinib Administration for Lung Cancer.

A 46-year-old woman with lung cancer who received chemotherapy was admitted to our hospital for lower-lobe bilateral ground-glass opacity (GGO). GGO developed after the lung cancer diagnosis, deteriorated after the initiation of osimertinib, and incompletely decreased after interrupting osimertinib; therefore, flexible bronchoscopy was performed. Transbronchial lung biopsy histology and anti-granulocyte/macrophage colony-stimulating factor autoantibody positivity revealed autoimmune pulmonary alveolar proteinosis (aPAP) that did not require treatment. This rare case of aPAP comorbid with lung cancer suggested that using PAP findings to differentiate from drug-induced lung injury or lymphangitis is difficult and that osimertinib was suspected to exacerbate aPAP.

Complete remission of pulmonary alveolar proteinosis after anti-tuberculous chemotherapy: a case report.

Pulmonary alveolar proteinosis (PAP) is a rare respiratory system disorder. Patients with PAP are at risk for a wide variety of secondary infections. This current case report describes a patient with PAP complicated by tuberculosis. A 48-year-old male patient with multiple follow-up chest computed tomography scans that showed predominant diffuse ground glass opacity in both lung fields, presented a few years later with new calcified lesions and pleural effusion. At this point, the associated auxiliary examination indicated the possibility of PAP combined with tuberculosis infection. The patient achieved complete remission after anti-tuberculosis treatment. PAP is an easily overlooked clinical syndrome due to its low prevalence and lack of specific clinical manifestations, especially when combined with other pulmonary lesions. Therefore, clinicians should consider this rare disease in patients presenting with pulmonary disease and plan for its co-morbidity with other secondary outcomes, such as opportunistic infections, which are a common and life-threatening complication in patients with PAP. This case indicates the possibility that anti-tuberculosis therapy can improve alveolar proteinosis in patients with PAP and secondary Mycobacterium tuberculosis infection.

An Infant With Interstitial Lung Disease of Rare Cause.

CASE PRESENTATION: An 11-month-old boy was admitted to our hospital because of "recurrent cough with intermittent dyspnea for more than 8 months, aggravated for 1 month." The baby began experiencing a recurrent milk-choking problem within 1.5 months after birth. He had been hospitalized four times, but the symptoms recurred. One month previously, the symptoms were aggravated and a chest CT scan performed at outside hospital showed interstitial changes. Pediatric bronchoscopy revealed bronchial inflammatory features, with hemosiderin-laden macrophages being found in BAL fluid (BALF). Also, periodic acid-Schiff (PAS) staining showed positive results, which indicated the possibility of pulmonary alveolar proteinosis (PAP) or idiopathic pulmonary hemosiderosis (IPH).

[Segmental Bronchoalveolar Lavage Provided a Favorable Clinical Course in a Case of Autoimmune Pulmonary Alveolar Proteinosis].

A 49-year-old man was diagnosed with autoimmune pulmonary alveolar proteinosis. Chest computed tomography (CT) showed typical CT findings of pulmonary alveolar proteinosis: thickening of septa with ground-glass opacities in both lung fields. The diagnosis of autoimmune pulmonary alveolar proteinosis (PAP) was based on findings of bronchoalveolar lavage (BAL) fluid with milky appearance and elevated serum titer of anti-granulocyte-macrophage colony-stimulating factor antibody. We decided to perform segmental BAL via bronchoscopy. The surgery was performed under a general anesthesia since the patient had severe hypoxemia and strong cough reflex. Following 3 repeated courses of therapy, his respiratory condition and the ground-glass opacity in both lung fields improved remarkably, with no recurrence in 3 years. There are only a few published case reports in the world of the usefulness of segmental BAL under general anesthesia for PAP. We consider that segmental BAL is a useful therapeutic method for PAP in cases with severe hypoxemia, such as the present patient.

Pulmonary Alveolar Proteinosis with Severe Respiratory Failure Improved by Segmental Lung Lavage with Fiberoptic Bronchoscopy under General Anesthesia.

Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous materials accumulate in the alveolar compartments. A 72-year-old man was diagnosed with autoimmune PAP with severe respiratory failure. We decided to perform segmental lung lavage (SLL) with fiberoptic bronchoscopy under general anesthesia. If improvement was not significant, whole-lung lavage (WLL) would be done. SLL improved the respiratory failure and computed tomography findings. This case showed improvement in not only the area where lavage was done but also the non-lavaged area. SLL with fiberoptic bronchoscopy under general anesthesia might be an appropriate treatment option for patients with severe PAP.