Pulmonary Alveolar Proteinosis: Clinical Features and Outcomes

doi:10.1378/chest.114.5.1357

Chest

Volume 114, Issue 5, November 1998, Pages 1357-1362

https://doi.org/10.1378/chest.114.5.1357 Get rights and content

Introduction

Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown etiology and variable natural history. To date, the largest series from a single institution has consisted of 68 individuals. To extend the understanding of the clinical features and natural history of PAP, we present a series of 24 patients with PAP from a single institution.

Methods

Patients with PAP were identified by a review of The Cleveland Clinic Foundation discharge database from 1965 to 1995. After identification, a chart review of the 24 selected patients was conducted. Charts were abstracted for historical, diagnostic, and therapeutic features. Diagnosis was confirmed by a review of the lung biopsy, where it was available, by a lung pathologist. Follow-up by telephone was performed with 19 patients.

Results

Most patients (70%) were male, and smoking was common (75%; mean pack-years, 29) in the group. The mean age at initial evaluation was 43 years. Presenting symptoms were as follows: 19 patients (79%) reported dyspnea, 19 patients (79%) reported a cough, 4 patients (17%) reported hemoptysis, and 3 patients (13%) reported chest pain. The earliest available spirometry after presentation of symptoms showed a prediction of mean FEV₁ of 74% (range, 45 to 99%) and a prediction of mean FVC of 76% (range, 41 to 99%). The diagnosis of PAP was established by transbronchial biopsy alone in 7 patients (29%) and by open-lung biopsy alone in 17 patients (71%). Whole lung lavage was deemed necessary in 13 patients (54%); 3 patients underwent lavage of one lung only, and 10 patients underwent bilateral whole lung lavage. Whole lung lavage was required only once in 46% of patients, and from two to four times in the remainder of patients. During the follow-up period (mean length of follow-up, 8.5 years; range, 5 months to 21 years), 25% of the patients died, but none as a result of sequelae of PAP. Half of the survivors reported persistent symptoms.

Conclusions

In this series, which represents one of the largest single institutional experiences with PAP reported, the clinical features are largely consistent with previously reported cases. However, contrary to early reported experiences in which open-lung biopsy was frequently required to establish PAP and in which whole lung lavage was needed, transbronchial biopsy established the diagnosis in 29% of patients and whole lung lavage could be deferred in 46% of patients.

Section snippets

Materials and Methods

To ascertain eligible cases, a list of patients designated under Diagnosis-Related Group 519.2 (PAP) in the hospital database was assembled. Inclusion criteria were the presence of PAP as confirmed by a physician diagnosis and a consistent lung biopsy. All available slides were reviewed by a lung pathologist (Dr. Farver) to confirm the diagnosis of PAP.

The medical records of eligible patients were reviewed by one of the study investigators, and data elements were extracted using a standard data

Results

Twenty-four patients with PAP were identified (17 were male, 7 were female). Their mean age (± SD) was 42 ± 13.5 years (range, 21 to 67 years of age), and 18 patients were current or former smokers at the time of the initial presentation (mean pack-years, 29). All patients were white. One of the following systemic diseases was present in each of five patients (21%): breast cancer, myelodysplasia, pericardial disease, inflammatory bowel disease, and prune belly syndrome. No patients were known

Discussion

This study extends the available experience with PAP (Table 1) and also makes several new observations. As in prior reports, PAP was more common among men than women, with typical onset in the fifth decade of life. As in the reports by Rosen et al¹ and Prakash et al,³ dyspnea also was a common presenting symptom among patients in the current series. Also, physical examination was largely unrevealing; the pulmonary physiologic profile of our patients was that of mild restriction with a

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Pulmonary alveolar proteinosis in Taiwan
2023, Journal of the Formosan Medical Association
Pulmonary alveolar proteinosis (PAP) is rare disease manifested as alveolar macrophage dysfunction and abnormal accumulation of surfactant protein in the alveoli. In this nationwide, population-based study, we investigated the epidemiology of PAP in Taiwan, and discovered the comorbidities and prognostic factors of PAP.
From the National Health Insurance Research Database (NHIRD), we obtained comprehensive information about all patients of PAP in Taiwan between 1995 and 2013. The incidence, baseline characteristics comorbidities, and prognostic factors of PAP were investigated.
The annual incidence rate of PAP was around 0.79 (range: 0.49–1.17) patients per million people after 2000, and the prevalence rate was 7.96 patients per million people by the end of 2013. In total, 276 patients of PAP were identified, including 177 (64%) and 99 (36%) patients with primary and secondary PAP, respectively. The median age of diagnosis was 53.8 years. The median survival was 9.6 years after the initial PAP diagnosis, and the 5-year survival rate was 65.96%. Twenty (7%) patients received whole lung lavage (WLL) within three months after the diagnosis had significantly better survival compared to the others. Multivariable Cox regression analyses showed that elder age, secondary PAP, and malignancy were associated with poorer survival, while WLL within 3 months of diagnosis might greatly improve the survival.
We demonstrated the epidemiology of PAP in Taiwan, showing several poor prognostic factors and the potential effectiveness of WLL. Further prospective studies based on registry are warranted to improve the diagnosis and treatment of PAP.
Sirolimus-induced secondary pulmonary alveolar proteinosis
2022, Respiratory Medicine Case Reports
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome that is characterized by the accumulation of excess surfactant in the alveolar space, leading to impaired gas exchange. Sirolimus-induced PAP is an extremely rare entity that has only been described in the literature in a small number of case reports. We present a case of a 39-year-old female with acute lymphocytic leukemia who underwent stem cell transplant, complicated by graft-versus-host-disease (GVHD) involving the skin for which she was treated with steroids, photopheresis, sirolimus, and ruxolitinib. She was admitted to the intensive care unit (ICU) for acute on chronic hypoxic respiratory failure requiring intermittent mechanical ventilation. Computed tomography (CT) of the chest showed thickened inter- and intralobular septa with ground glass opacities and consolidation with a limited geographic pattern. Bronchoalveolar lavage fluid was stained with Periodic acid-Schiff (PAS), which was positive for extracellular proteinaceous material. Autoimmune studies including antibody levels for primary autoimmune pulmonary alveolar proteinosis (PAP) were negative. The patient was diagnosed with sirolimus-induced secondary PAP, and sirolimus was discontinued. A year later, she no longer required supplemental oxygen, and repeat CT imaging showed only faint residual disease. This is the only documented case of sirolimus-induced PAP in a stem cell transplant recipient and the first case reported in which the patient developed severe hypoxic respiratory failure requiring mechanical ventilation. In the right clinical context, PAP can be diagnosed with characteristic high resolution computed tomography (HRCT) findings, serum GM-CSF antibody levels, and bronchoscopy with bronchoalveolar lavage.
Diagnostic yield and safety of bronchofiberscopy for pulmonary alveolar proteinosis
2021, Respiratory Investigation
Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. If high-resolution computed tomography (HRCT) indicates the presence of PAP, a definitive diagnosis of PAP is established when consistent pathological findings are obtained. Herein, we retrospectively studied the yield and safety of bronchofiberscopy in the diagnosis of PAP.
One hundred and fifty consecutive patients with PAP were prospectively registered in the PAP cohort database of the National Hospital Organization Kinki-Chuo Chest Medical Center between January 1991 and December 2018. We examined 86 patients who underwent bronchofiberscopy with bronchoalveolar lavage (BAL) and transbronchial lung forceps biopsy (TBLB).
The patients included 56 men and 30 women, with a median age of 57 years. All patients had autoimmune PAP, and the median level of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies was 42.8 μg/mL. The diagnostic yield was 90.7% (78/86) with BAL and 81.4% (70/86) with TBLB. The combination of BAL and TBLB increased the yield to 98.8%. Age, disease severity score, and frequency of traction bronchiectasis on HRCT were significantly different between the TBLB-positive and TBLB-negative groups. No patient developed serious complications due to bronchofiberscopy; TBLB-related complications included pneumothorax (3.5%) and minimal bleeding (7.0%).
Bronchofiberscopy, in combination with BAL and TBLB, is an effective and safe method for the diagnosis of PAP, with a yield of 98.8%.
Pulmonary Alveolar Proteinosis
2021, Encyclopedia of Respiratory Medicine, Second Edition
Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome characterized by the accumulation of surfactant in the alveolar space resulting in impaired gas exchange. Primary PAP, the most common form of disease, is caused by disruption in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling due to acquired neutralizing autoantibodies. PAP often presents as progressive dyspnea of insidious onset with a widely variable clinical course, ranging from spontaneous remission to respiratory failure and death. While whole lung lavage remains the mainstay of therapy, there are several proposed novel and promising targeted therapies.
Orphan Lung Diseases
2019, Medical Clinics of North America
Citation Excerpt :
There does not seem to be an ethnic predilection and large series have been reported from Iran, Israel, Japan, and the United States. The most common presenting symptom is dyspnea, which is seen in 54.3% to 79.0% of the patients.15,21 Cough, hemoptysis, and chest pain are present in 79%, 17%, and 13% of the patients, respectively.
Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach
2018, The Lancet Respiratory Medicine
Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages due to abnormal surfactant homoeostasis. Identification of the granulocyte–macrophage colony-stimulating factor (GM-CSF) as an indispensable mediator of macrophage maturation and surfactant catabolism was the key discovery leading to the current understanding of the pathogenesis of most forms of PAP. Impaired GM-CSF bioavailability due to anti-GM-CSF autoimmunity is the cause of approximately 90% of adult PAP cases. Abnormal macrophage function due to endogenous or exogenous triggers, GM-CSF receptor defects, and other genetic abnormalities of surfactant production account for the remainder of causes. The usual physiological consequence of PAP is impairment of gas exchange, which can lead to dyspnoea, hypoxaemia, or even respiratory failure and death. Pulmonary fibrosis occurs occasionally in patients with PAP. For patients with moderate to severe disease, whole lung lavage is still the first-line treatment of choice. Supplemental GM-CSF is also useful, but details about indications, choice of agent, and dosing remain unclear. Other therapies, including rituximab, plasmapheresis, and lung transplantation have been described but should be reserved for refractory cases.

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Clinicai Investigations: Important TopicsPulmonary Alveolar Proteinosis: Clinical Features and Outcomes

Introduction

Methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Mayo Clin Proc

Br J Dis Chest

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Dis Chest

Ann Thorac Surg

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