Pulmonary Alveolar Proteinosis-PAP Samples

Bay Biosciences provides high quality, clinical grade bio-samples, cryogenically preserved bronchoscopy, transbronchial biopsy tissue, bronchoalveolar lavage (BAL), sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid specimens from patients diagnosed with Pulmonary Alveolar Proteinosis (PAP) Disease.

The sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid samples are processed from patient’s peripheral whole-blood using customized processing protocols. The Pulmonary Alveolar Proteinosis (PAP) Disorder bio-specimens are collected from unique patients diagnosed with Pulmonary Alveolar Proteinosis (PAP) Disorder and are provided to a valued pharmaceutical customer for translational research, genomics, proteomics and biomarker research, drug discovery and development.

Pulmonary Alveolar Proteinosis (PAP) Overview

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by an abnormal accumulation of surfactant-derived lipoprotein compounds (buildup of proteins, fats and other substances) within the alveoli of the lungs, alveoli are the part of the lungs that contain air, and its there that gases between the lungs ad the blood are exchanged. The accumulated substances interfere with the normal gas exchange and expansion of the lungs, ultimately leading to difficulty breathing and a predisposition to developing lung infections. The causes of PAP may be grouped into primary (autoimmune PAP, hereditary PAP), secondary (multiple diseases), and congenital (multiple diseases, usually genetic) causes, although the most common cause is a primary autoimmune condition in an individual.

Pulmonary Alveolar Proteinosis (PAP) condition happens more often in men than in women. It usually affects people between the ages of 30 and 60. Exposures like dusts and smoking increase the risk of PAP, which may explain why it has been recognized more often in men. Pulmonary Alveolar Proteinosis (PAP) is a rare disease, affecting about 1 person in 100,000 people worldwide, with fewer than 10,000 of them in the U.S. It generally develops in adults, but it can be congenital (something you are born with). Pulmonary Alveolar Proteinosis (PAP) It is also known as phospholipidosis or pulmonary alveolar lipoproteinosis.

Types of Pulmonary Alveolar Proteinosis (PAP)

Pulmonary Alveolar Proteinosis (PAP) Types include:

• Autoimmune Pulmonary Alveolar Proteinosis (aPAP): This type is the most common and is believed to represent about 90% of adults who get it. These adults are mostly between the ages of 30 and 60 years old.
• Secondary PAP: This type is a result of having another type of disease or condition or of being exposed to a toxin of some type.
• Congenital: There is a form of PAP that happens because of genetic defects passed down in families.

Pulmonary Alveolar Proteinosis (PAP) Signs & Symptoms

Pulmonary Alveolar Proteinosis (PAP) has the following general symptoms:

• Shortness of breath (Dyspnea)
• Fingertips bluish in color (cyanosis)
• Cough
• Chest pain or tightness
• Fever
• Weight loss
• Low levels of oxygen in the blood
• Nail clubbing (abnormal growth of toenails or fingernails)

Autoimmune Alveolar Proteinosis (PAP) Symptoms:

In Autoimmune Pulmonary Alveolar Proteinosis (PAP), a feeling shortness of breath (dyspnea) is the most common symptom. Most patients develop dyspnea very slowly over time, typically noticing it only with activity at first and eventually also at rest. As the disease gets worse from the buildup of surfactant, the fingertips can become bluish in color (cyanosis) due to a low level of oxygen in the blood.

Cough is the next most common symptom. This can be a dry cough or a productive cough that produces whitish phlegm (sputum). Coughing up phlegm with streaks of blood (hemoptysis), with or without fever, usually indicates that infection is also present. Rounding of the fingernails and swelling of the finger tips (clubbing) is not a sign of autoimmune PAP. Fatigue, weight loss, chest pain, or a general feeling of ill health (malaise) can also occur. Less commonly, secondary infections can occur in or outside the lungs.

The disease activity over time (natural history) varies among patients with some experiencing life-threatening respiratory failure while others having a ‘smoldering’ or slowly progressing course and some others may undergo spontaneous improvement. At any given time, about thirty percent of patients may not have any symptoms and the disease is discovered accidentally (incidental).

Hereditary Alveolar Proteinosis (PAP) Symptoms:

Hereditary Pulmonary Alveolar Proteinosis (PAP) disease is caused by genetic mutations that disrupt the structure of GM-CSF receptors (proteins) on alveolar macrophages, which normally bind GM-CSF and function in an ‘ignition switch’ and ‘car key’ allowing GM-CSF to stimulate these cells. The genetic mutations prevent GM-CSF receptors from functioning normally and thus block the effects of GM-CSF on surfactant removal by alveolar macrophages. The clinical presentation of hereditary PAP is similar to that of autoimmune PAP except that it usually develops in children between the ages of 1 and 10 years of age but occasionally occurs in adolescents and older adults. The natural history is also similar to that of autoimmune PAP except that spontaneous improvement has not been reported.

Secondary Alveolar Proteinosis (PAP) Symptoms:

In Secondary Pulmonary Alveolar Proteinosis (PAP), the presentation is similar to that of primary PAP but occurs in individuals with another underlying disease (or toxic exposure) known to cause PAP. The natural history typically follows the clinical course of the underlying disease.

Congenital Alveolar Proteinosis (PAP) Symptoms:

In Congenital Pulmonary Alveolar Proteinosis (PAP), the clinical presentation depends on which genetic mutation is present. It can vary from respiratory failure at birth to slow development of lung scaring (fibrosis) in children, adolescents, or adults. Symptoms can include rapid breathing (tachypnea), difficulty gaining weight, and fever. This is usually an indication that infection is present. The natural history, although poorly studied, may involve worsening of disease over time and progression to respiratory failure at various ages, depending on the specific gene involved and mutation present.

Pulmonary Alveolar Proteinosis (PAP) Causes

In the majority of Pulmonary Alveolar Proteinosis (PAP) cases in adults, the cause is suspected to be a lack of or a problem with granulocyte-macrophage colony-stimulating factor (GM-CSF). This substance is needed to make certain immune cells develop. Without it, the air sacs are not able to clear out all traces of protein-containing materials. This leads to accumulation of debris in the air sacs and eventually to breathing problems.

Primary Pulmonary Alveolar Proteinosis (PAP) is caused by reduced GM-CSF stimulation of alveolar macrophages, which reduces their ability to remove surfactant from alveoli and results in surfactant build up and breathlessness. Since GM-CSF is also necessary to help alveolar macrophages (and white blood cells) kill and remove bacteria and viruses, loss of GM-CSF stimulation can also result in secondary infections.

Primary Pulmonary Alveolar Proteinosis (PAP) includes two diseases:

Autoimmune Pulmonary Alveolar Proteinosis (PAP) and

Hereditary Pulmonary Alveolar Proteinosis (PAP)

Autoimmune Pulmonary Alveolar Proteinosis (PAP), the body’s immune cells (B cells) begin making a protein (GM-CSF autoantibody) that attacks GM-CSF and blocks its ability to stimulate alveolar macrophages. While it is known how GM-CSF autoantibodies cause disease (pathogenesis), it is not known what causes the disease to start (etiology). However, PAP occurs more commonly in smokers suggesting cigarette smoking is a ‘trigger’ for the disease.

Hereditary Pulmonary Alveolar Proteinosis (PAP), individuals are born with genetic mutations that destroy the function of proteins (receptors) on alveolar macrophage that interact with GM-CSF. The loss of GM-CSF receptor function blocks the ability of GM-CSF to stimulate alveolar macrophages. Hereditary Pulmonary Alveolar Proteinosis (PAP) is a recessive genetic disorder determined by inheritance of traits from each parent. Here, the trait (specific characteristic) is abnormal GM-CSF receptor function caused by the presence of a specific gene mutation.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

Secondary Pulmonary Alveolar Proteinosis (PAP), an underlying disease or clinical condition causes a reduction in the number (or function) of alveolar macrophages, which in turn results in the buildup of surfactant in alveoli and shortness of breath. Many diseases or toxic substance exposures are associated with secondary Pulmonary Alveolar Proteinosis (PAP). Examples include myelodysplasia (most common), HIV infection, chemotherapy and inhalation of dusts (silica, titanium, aluminum, others).

Congenital Pulmonary Alveolar Proteinosis (PAP), individuals are born with genetic mutations that disrupt the production of normal surfactant. These include genes coding for surfactant protein B (SFTPB), surfactant protein C (SFTPC), a protein involved in lung development (NKX2.1), a protein needed for inclusion of surfactant lipids (ABCA3), and probably other undiscovered genes. These mutations lead to production of abnormal surfactant. This buildup in the alveoli results in PAP, but also has more important harmful effects including alveolar collapse, alveolar scarring and distortion (interstitial fibrosis) that can result in reduced lung function or respiratory failure. Some forms of congenital PAP are caused by recessive genetic mutations (see above) while others are caused by dominant genetic mutations in which only one of the inherited genes is abnormal and the other is normal.

Detailed clinical data, CT, MRI HRCT scans, cerebrospinal fluid/blood analysis, blood test measuring gas levels, pulmonary function test (PFT) results, elevated biomarker levels, bronchoscopy, transbronchial  genetic and metabolic information, histopathological findings, annotations associated with the Pulmonary Alveolar Proteinosis (PAP) Disorder patient’s specimens is provided to a valued customer for research, development and drug discovery.

The Pulmonary Alveolar Proteinosis (PAP) Disorder (BAL), sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid samples are processed from patients peripheral whole-blood using customized collection and processing protocols provided by the researcher.