Pulmonary alveolar proteinosis: symptoms, diagnosis and treatment

The lungs contain millions of tiny air sacs called alveoli, where oxygen passes into the blood. Royal Brompton & Harefield hospitals explain that in pulmonary alveolar proteinosis the alveoli do not work properly because they become filled with an oily, protein-type material called surfactant. Surfactant normally lines the air sacs and helps them stay open, but in PAP it either builds up in excess or is not cleared properly.

As a result, the lungs cannot get oxygen into the bloodstream as easily as normal, which leads to breathlessness, coughing and chest pain. The clinical reference article on Patient.info, written by UK doctors for health professionals, adds that the lungs become stiff, with restricted ventilation, and that secondary infection may occur.

PAP is not a form of cancer and it is not contagious. It is one of a group of rare conditions of the lung tissue that respiratory specialists manage.

Royal Brompton says there have been big advances in understanding PAP in the past decade and that several distinctly different forms are now recognised. They are summarised here from the hospital’s page and from the clinical article.

Royal Brompton says most people diagnosed with PAP have some of a typical set of symptoms, though the combination varies. The clinical article adds that people usually present between 20 and 50 years of age, that onset is typically gradual, and that as many as 30% of patients may have no symptoms at all even when the chest X-ray is abnormal.

• Breathlessness, either on activity or sometimes at rest.

• A decreasing ability to exercise.

• Cough, sometimes with white or yellowish phlegm; the clinical article describes a persistent dry cough as typical.

• Chest pain of varying degree.

• Fever or sweats.

• Generalised aches and pains.

• Fatigue, tiredness, low mood or anxiety.

Royal Brompton explains that people with the symptoms above usually see their GP first. If symptoms are severe, they are referred for tests at a local hospital; if milder, a GP may recommend healthy lifestyle changes such as stopping smoking and then refer to hospital if there is no improvement. Breathlessness that is new, getting worse or limiting your day should always be assessed, and sudden severe breathlessness, blue lips or chest pain that does not settle needs 999.

The hospital states that X-rays are the initial test, and that if results are abnormal further specialist investigations such as bronchoscopy are done. The clinical article lists the investigations used in practice: a chest X-ray showing bilateral shadowing, a high-resolution CT scan, which often shows a pattern called crazy-paving, bronchoscopy with washing of the airways (bronchoalveolar lavage), a raised blood lactate dehydrogenase level, and sometimes a lung biopsy. It also says tests for anti-GM-CSF antibodies are under investigation as a more effective diagnostic approach.

The clinical article notes that these appearances can be similar to those of other conditions, such as sarcoidosis, hypersensitivity pneumonitis or infection, which is why a specialist respiratory team is involved.

The clinical article says that people with minimal symptoms may need only symptomatic treatment, while those with low blood oxygen need more active management, along with treatment of any underlying cause. Royal Brompton lists physiotherapy, cough medicines, washing the lungs and medication as options.

Whole-lung lavage is described as the most widely accepted treatment for symptomatic PAP. It is done under general anaesthesia: one lung is ventilated with 100% oxygen while the other is washed with saline, a process that can take several hours. The article says it is usually very effective but that repeat lavages are often needed. GM-CSF replacement has emerged as an alternative and has shown promise in acquired cases, and lung transplantation is considered for congenital PAP or end-stage lung scarring. Steroids and aerosol mucolytics have in the past been used without much success.

People whose PAP is related to inhaled dusts or insecticides are advised to avoid further exposure.

The clinical article describes the outlook as varying with the underlying cause. In about a third of patients no appreciable disability develops and the disease remits spontaneously or fails to progress. It gives estimates of 5-year mortality that vary between 10% and 30%, and these come from older data. Whole-lung lavage often produces a dramatic response, though recurrences are common.

Complications listed include lung infections with organisms such as Nocardia, Pneumocystis jirovecii and Mycobacterium avium, as well as pulmonary fibrosis and pulmonary hypertension. Tell your care team promptly about fever, a change in sputum or worsening breathlessness, as infections may need prompt treatment.

Because PAP is so rare, Royal Brompton notes that few doctors have experience of managing it and even some specialist centres see only small numbers of patients. Referral to a specialist centre, often arranged by your respiratory consultant, is the usual route in the NHS. Travel to a specialist centre may be needed for lavage, with a planned admission lasting a few days.

Practical steps include not smoking, avoiding dusty or fume-filled environments, asking your clinicians which vaccinations are advised for you, and recording changes in breathlessness. Patient groups, including a US-based foundation mentioned by Royal Brompton, offer information and peer support. Private respiratory consultations are available and can speed up initial assessment, but whole-lung lavage is a specialist procedure available in a limited number of centres.