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Interstitial Lung Disease

AYESHA FAREEDPHARM D

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•Interstitial lung disease is a general category that includes many different lung conditions. •All interstitial lung diseases affect the interstitium, a part of the lungs anatomic structure.•The interstitium is a lace-like network of tissue that extends throughout both lungs.• The interstitium provides support to the lungs microscopic air sacs (alveoli),Tiny blood vessels travel through the interstitium, allowing gas exchange between blood and the air in the lungs. •Normally, the interstitium is so thin it can't be seen on chest X-rays or CT scans.

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Types of Interstitial Lung Disease:

•All forms of interstitial lung disease cause thickening of the interstitium. The thickening can be due to inflammation, scarring, or extra fluid (edema).• Some forms of interstitial lung disease are short-lived; others are chronic and irreversible.Some of the types of interstitial lung disease include:

•1.Interstitial pneumonia: Bacteria, viruses, or fungi may infect the interstitium of the lung. A bacterium called Mycoplasma pneumonia is the most common cause.•2.Idiopathic pulmonary fibrosis : A chronic, progressive form of fibrosis (scarring) of the interstitium. Its cause is unknown.

•3.Nonspecific interstitial pneumonitis: Interstitial lung disease that's often present with autoimmune conditions (such as rheumatoid arthritis or scleroderma).

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4.Hypersensitivity pneumonitis: Interstitial lung disease caused by ongoing inhalation of dust, mold, or other irritants.

5.Cryptogenic organizing pneumonia (COP): A pneumonia-like interstitial lung disease but without an infection present. COP is also called bronchiolitis obliterans with organizing pneumonia (BOOP).

6.Acute interstitial pneumonitis: A sudden, severe interstitial lung disease, often requiring life support.

7.Desquamative interstitial pneumonitis: An interstitial lung disease that's partially caused by smoking.

8.Sarcoidosis: A condition causing interstitial lung disease along with swollen lymph nodes, and sometimes heart, skin, nerve, or eye involvement.

9. Asbestosis: Interstitial lung disease caused by asbestos exposure.

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Causes of Interstitial Lung Disease:•Bacteria, viruses, and fungi are known to cause interstitial pneumonias. •Regular exposures to inhaled irritants at work or during hobbies can also cause some interstitial lung disease. These irritants include:AsbestosSilica dustTalcCoal dust, or various other metal dusts from working in miningGrain dust from farmingBird proteins (such as from exotic birds, chickens, or pigeons)Drugs such as nitrofurantoin, amiodarone, bleomycin, and many others can rarely cause interstitial lung disease.Men and women of any age can be affected. Interstitial lung disease is more common in people with autoimmune disease, including lupus, rheumatoid arthritis, and scleroderma.

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The most common symptom of all forms of interstitial lung disease is• shortness of breath, Nearly all people with interstitial lung disease will experience breathlessness, which may get worse over time.

Other symptoms of interstitial lung disease include:•Cough, which is usually dry and nonproductive.•Weight loss, most often in people with COP or BOOP.

•In most forms of interstitial lung disease, the shortness of breath develops slowly (over months).• In interstitial pneumonias or acute interstitial pneumonitis, symptoms come on more rapidly (in hours or days).

symptoms

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Risk factors:Factors susceptible to interstitial lung disease include:

Age. Interstitial lung disease is much more likely to affect adults, although infants and children are sometimes affected.Exposure to occupational and environmental toxins. people work in mining, farming or construction or for any reason are exposed to environmental agents known to damage lungs.Family history. There is evidence that some forms of interstitial lung disease are heritable and risk of developing it is increased if close family members have the disease.Radiation and chemotherapy/immunomodulatory drugs: Having radiation treatments to chest or using some chemotherapy or immunomodulatory drugsSmoking. Some forms of interstitial lung disease are more likely to occur in people with a history of smoking, and active smoking may make the condition worse, especially if there is associated emphysema.

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ComplicationsAcute exacerbation: Acute exacerbation can occur unexpectedly and often requires hospitalization with supportive management. It is a serious complication found in many types of interstitial lung disease.

Gastro esophageal reflux disease (GERD). Recent studies suggest that GERD is associated with a more rapid progression of idiopathic pulmonary fibrosis, a specific form of interstitial lung disease. High blood pressures in the vessels of the lungs (pulmonary hypertension. Pulmonary hypertension is a serious illness that becomes progressively worse, leading to failure or dysfunction of the right side of the heart (cor pulmonale).

Low oxygen (hypoxemia). As lung disease progresses, oxygen support may be required both at rest and with exertion.

Respiratory failure. In the end stage of chronic interstitial lung disease, respiratory failure occurs when severely low blood oxygen levels along with rising pressures in the pulmonary arteries and the right ventricle cause heart failure.

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Diagnosis of Interstitial Lung Disease:People with interstitial lung disease usually come to see a doctor due to concern about shortness of breath or cough. Imaging tests of the lungs are usually done to identify the problem.

Chest X-ray:  Chest X-ray films in people with interstitial lung disease may show fine lines in the lungs.Computed tomography (CT scan):  Interstitial lung disease can usually be seen on a CT scan.High-resolution CT scan: If interstitial lung disease is suspected, using certain CT scanner settings can improve the images of the interstitium. This increases the CT scan's ability to detect interstitial lung disease.Pulmonary function testing: People with interstitial lung disease may have a reduced total lung capacity. They may also have a decreased ability to transfer oxygen from their lungs into their blood

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Lung biopsy: Often, obtaining lung tissue to examine under a microscope is the only way to determine which type of interstitial lung disease a person has. There are several ways to collect lung tissue, which is called a lung biopsy.•Bronchoscopy: An endoscope is advanced through the mouth or nose into the airways. Tiny tools on the endoscope can take a sample of lung tissue.•Video-assisted thoracoscopic surgery (VATS): Using tools inserted through small incisions, a surgeon can sample multiple areas of lung tissue.•Open lung biopsy (thoracotomy): In some cases, traditional surgery with a large incision in the chest is needed to obtain a lung biopsy.

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Treatments for Interstitial Lung DiseaseTreatments for interstitial lung disease vary according to the type of interstitial lung disease and its cause.Antibiotics: These are effective treatments for most interstitial pneumonias.•Azithromycin and levofloxacin eliminate the bacteria that cause most interstitial pneumonias. •Viral pneumonias usually resolve on their own. Fungal pneumonias are rare, but can be treated with antifungal drugs.Corticosteroids: In some forms of interstitial lung disease, ongoing inflammation in the lungs causes damage and scarring. Corticosteroids like prednisone and methylprednisolone reduce the activity of the immune system. This reduces the amount of inflammation in the lungs and the rest of the body.Inhaled oxygen: In people with low oxygen blood levels due to interstitial lung disease, inhaled oxygen may improve symptoms. Regular use of oxygen might also protect the heart from damage caused by low oxygen levels.

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Lung transplant: In advanced interstitial lung disease causing severe impairment, a lung transplant may be the best option. Most people undergoing lung transplant for interstitial lung disease make large gains in quality of life and their ability to exercise.Azathioprine (Imuran): This drug also suppresses the immune system. It has never been proven to improve interstitial lung disease, but some studies suggest it might help.N-acetylcysteine (Mucomyst): This potent antioxidant may slow the decline of lung function in some forms of interstitial lung disease. It does not improve people's survival from interstitial lung disease.

Other less often-used treatments for interstitial lung disease include:Cyclophosphamide (Cytoxan)MethotrexateCyclosporineThese medicines suppress the immune system significantly. They may be used in some cases of interstitial lung disease while monitoring for side effects.

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Oxygen therapyUsing oxygen can't stop lung damage, but it can:•Make breathing and exercise easier•Prevent or lessen complications from low blood oxygen levels•Reduce blood pressure in the right side of your heart•Improve your sleep and sense of well-being•You're most likely to receive oxygen when you sleep or exercise, although some people may use it round-the-clock.

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Antibiotics:Azithromycin: macrolide antibioticDose : 500mg given orally once daily, then 250mg once daily for 4days. Later, alternate 500mg per oral once daily for 3 daysADR: diarrhea (52.8%) nausea(32.6%) abdominal pain(27%)Monitoring : LFTs, ECG (QT prolongation)Pharmacodynamics: t half: 70hrs bioavailability: 37%

Levofloxacin: floroquinolones Dose: 500mg per oral or IV once daily for 7-14 daysADR: nausea, headache, diarrhea (1-10%) Monitoring: ECG (QT prolongation)Pharmacodynamics: t half: 6-8hrs bioavailability: 99%

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Prednisolone:Dose:0.5 mg/kg to start, tapering over 3 months to 10-20mg/day maintenance dose

Monitoring: blood glucose levels, electrolytesADRs: adrenal suppression, glucose intolerancePharmacodynamics: t half: 3-4 hrs

Azathioprine: immunosuppressantDose: 2mg/kg/day to maximum of 150mgSide effects: amaemia, bone marrow suppression, alopeciaMonitor: epistaxis, mouth ulcer bleedingWithhold :ifWhite cell count:<4x 10⁹/LNeutrophil count: <2x 10⁹/LPlatelet count: <150 x 10⁹/LAST/ALT: >2 times the upper limit of normalUrea and creatinine rising without any alternative explanation

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Cyclosporine: (immunosuppressant)Dose:4-12hr pre transplant : 15mg/kg per oral for 1 dose1-2 week post transplant:15mg/kg/day per oral twice dailyMaintenance dose: 12.5mg/kg/day (↑FVC) in 10% casesPharmacodynamics: t half: 8.4- 27hrs

Methotrexate:It is used in RA associated ILD but <70% chances of causing pulmonary impairmentDrug induced ILD?

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Cyclophosphamide:

Dose: 2mg/kg/day 3-4 weekly regimen over at least 6 months. In some cases it is continued up to a yearADR: thrombocytopenia, bleeding, infertility, hair lossMonitor: secondary malignancies, LFT, renal function, CBCPharmacodynamics: t half: 3-12hrs bioavailability: 75%

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COMBINATION THERAPY:

•Start Prednisolone first at dose of 0.5mg/kg/day tapering over 3 months to 10-20mg/day maintenance.

•After 1 month start azathioprine at a dose of 50mg daily with weekly blood tests. if blood remain stable increase the dose by 50mg increments every month to a maximum dose of 150mg daily.

•After a further month add in NAC at full dose (600mg daily)•All 3 drugs should be continued for long time

•Monitoring: CBC,LFT, every week for first 4 weeks, then every 2 weeks for the next month, reducing it to every 3 months once stable dosing has been achieved.

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•Cyclosporine 7mg/kg/day and prednisolone 20mg/day theses doses are maintained for 8-10 weeks and reduced over following 2months to

• maintenance dose of 3mg/kg/day of of cyclosporine and 10mg/day of prednisolone.

This combination decreased the dysponea and increased FVC

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Lifestyle and home remedies:

•Stop smoking. If you have lung disease, the best thing you can do for yourself is to stop smoking. •Eat well. People with lung disease may lose weight both because it's uncomfortable to eat and because of the extra energy it takes to breathe. •These people need a nutritionally rich diet that contains adequate calories. A dietitian can give you further guidelines for healthy eating.•Remain active. As much as you can tolerate, continue to exercise and remain active to avoid deconditioning.•Get vaccinated. Respiratory infections can worsen symptoms of interstitial lung disease. Make sure you receive the pneumonia vaccine and an annual flu shot.

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•Mason, R. Murray and Nadel's ,Textbook of Respiratory Medicine, 4th edition, Elsevier Saunders, 2005.

•National Jewish Health: "Interstitial Lung Disease (ILD): Overview."FamilyDoctor.org: "Occupational Respiratory Disease.“ News release, FDA.Reviewed by Varnada Karriem-Norwood, MDon July 15.

•J A moolman et al. cyclosporine as a treatment fot interstitial lung disease of unknown aetiology:1991;46:592-595.

•Buckinghamshire hospitals NHS trust, department of respiratory medicine,azathioprine,prednisolone,and Nacetyl cysteine in interstitial lung disease; guidelines for prescribing and ss at <<http://www.brit-thoracic.org.uk>>

References:

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