​Kembara Xtra - Medicine - Interstitial Lung Disease

​Kembara Xtra - Medicine - Interstitial Lung Disease 
Introduction 
Interstitial lung diseases (ILDs) are a broad category of chronic progressive lung disorders linked to pulmonary fibrosis and/or alveolar inflammation that may be irreversible.
More than 200 different diseases may appear with similar symptoms, making it challenging to classify ILD. These subtypes are part of a classification system that the American Thoracic Society and European Respiratory Society have suggested:
- Known causes (diseases linked to drugs, the workplace, or the environment)
Systemic illnesses, such as sarcoidosis, Wegener granulomatosis, and collagen vascular disease
- Infrequent lung conditions, such as lymphangioleiomyomatosis and pulmonary histiocytosis
- Interstitial pneumonias with no known cause (IIPs)
IIPs are further divided into the following diagnosis based on clinical, radiologic, and histologic characteristics:
- Major IIPs, including respiratory bronchiolitis-associated ILD (cryptogenic organizing pneumonia [COP]), nonspecific interstitial pneumonia (NSIP), and idiopathic pulmonary fibrosis (IPF).
IIP classification and the linkages between the subtypes are challenging to categorize because of the varied patterns of injury.
Child Safety Considerations
Children and infants with ILD are affected by a variety of respiratory conditions. Diseases are caused by a variety of processes, some of which are separate from those that result in ILD in adults and involve genetic variables, inflammatory, or fibrotic responses. Some diseases are brought on by afflictions with early growth and development.

Incidence and prevalence in Epidemiology 
Incidence
Because case definitions and diagnostic techniques vary, it is challenging to pinpoint incidence and prevalence precisely. Incidence in the US: 16.3 to 17.4 Prevalence
In the US, prevalence ranges from 42.7 to 63 cases per 100,000 people in the general population, while pediatric ILD affects 3.6 million people.

Pathophysiology and Etiology 
Variable levels of ventilatory dysfunction occur among the ILD subtypes, and alveolar inflammation may develop into permanent fibrosis.
ILD that is linked to systemic connective diseases and collagen vascular disease can show involvement of the musculoskeletal, ocular, and skin systems. Specific exposures are linked to certain ILD types:
Amiodarone, antibiotics [particularly nitrofurantoin], chemotherapy drugs, gold, and illegal narcotics are examples of medications. Inorganic dusts include silicates, asbestos, talc, mica, coal dust, and graphite. Organic dusts include moldy hay, inhaling fungi, bacteria, and animal proteins.
- Metals (barium, cobalt, tin, aluminum, and cobalt) - Gases, fumes, vapors, and aerosols
Genetics
Unknown are the effects of genetic variables.

Risk factors include: exposure to inorganic or organic dusts in the environment or at work; smoking history; and 66-75% of patients with ILD. Age is not a good indicator of pathology due to the variety of diseases:
- Between the ages of 20 and 40, the majority of patients with hereditary subtypes and pathology associated with connective tissue disease present.
- The median age of IPF patients is 66 years old. Studies examining age, ethnicity, and smoking status as clinical determinants of survival have produced mixed results.

Accompanying Conditions 

ILD is linked to numerous primary illnesses and systemic conditions. Following is a sample of the list:
Sarcoidosis, Amyloidosis, Goodpasture syndrome, Churg-Strauss syndrome, Wegener granulomatosis, Collagen vascular disease,


Diagnosis 
The absence of other known ILD causes, the presence of a UIP pattern on high-resolution computed tomography (HRCT), and/or a surgical lung biopsy pattern are all necessary for the diagnosis of IPF.


History-telling Progression of exertional dyspnea and nonproductive cough; possible hemoptysis or fatigue
Some cases of lung disease may occur weeks to years after discontinuing an offending agent. Acquiring a history of the illness duration (acute vs. chronic), possible environmental/occupational exposures, travel, medical conditions (including systemic diseases), and medication reconciliation is important in assessing the cause of the ILD.

clinical assessment 
The majority of physical findings are nonspecific. The following are some typical traits:
Inspiratory "squeaks" Clubbing of the digits and cyanosis in advanced disease Fine crackles (usually present on auscultation of lung bases on posterior axillary line)

Differential diagnosis: lymphatic tumor spread or diffuse bronchoalveolar cell cancer; acute pulmonary edema; diffuse bleeding; atypical pneumonia.

Laboratory Results 

Initial examinations (lab, imaging)
O2 saturation, peak expiratory flow rate, a CBC with differential, a thorough metabolic profile, erythrocyte sedimentation rate (ESR), and a chest x-ray (CXR) with reticular, less frequently nodular, or mixed patterns are all indicators of health.


Tests in the Future & Special Considerations

The most effective method for identifying and classifying ILD subclasses is HRCT of the chest, especially when CXRs are normal:

 If necessary, plasma ACE inhibitor concentration (sarcoidosis), hypersensitivity pneumonitis panel, and arterial blood gas (ABG)
Consider antinuclear antibody (ANA), rheumatoid factor (RF), antineutrophil cytoplasmic antibodies (ANCA), anti-cyclic citrullinated peptide (anti-CCP), and a myositis panel if a systemic illness is suspected.

Other/Diagnostic Procedures

The forced vital capacity (FVC), which is measured using the pulmonary function test (PFT; also known as spirometry, lung volumes, and carbon monoxide diffusing capacity), frequently shows a restrictive defect (decreased vital capacity and total lung capacity) in IPF patients who are receiving a placebo in clinical trials.
In order to identify between subgroups (such as sarcoidosis, hypersensitivity pneumonitis, and cancer), bronchoscopy - Bronchoalveolar lavage (BAL) cellular analysis investigations may be helpful. If performed, the HRCT result should be used to determine the BAL target location.
– The diagnosis of sarcoidosis may be aided by bronchoscopy-guided transbronchial lung biopsy, which can also occasionally be adequately supportive of other ILD diagnoses.
Since HRCT has better specificity, it may be advised if a diagnosis cannot be made via transbronchial biopsy or HRCT Test Interpretation. Thoracoscopic surgery for lung biopsy has the highest diagnostic specificity for ILDs but is less frequently utilized.
IIP diagnostic categories are based on the histopathologic patterns discovered during lung biopsy.
It may be possible to discriminate between the following subtypes using characteristic alterations on HRCT:
- In later phases, honeycombing and reticulonodular opacities may be visible.
No particular test is the gold standard, which highlights the significance of a multidisciplinary consensus for diagnosis with clinical, radiologic, and pathologic findings. Stage I and II sarcoidosis are marked by associated hilar and mediastinal adenopathy.

Management 

There is no evidence to support the routine application of any particular therapy for ILD in general, particularly IPF. Using home oxygen does not improve survival in ILD.

Some ILD subtypes are affected by corticosteroids.

Current evidence does not clearly support the routine use of noncorticosteroid anti-inflammatory drugs, such as cyclosporine, colchicine, cyclophosphamide, cytokines, sildenafil, dual endothelin receptor antagonists (bosentan, macitentan), etanercept, methotrexate, or interferon, for IPF. Current evidence also does not support the use of antibiotics, specifically co-trimo
Despite early promise in a small historical control trial, thrombomodulin alfa proved ineffective in improving 3-month survival after acute exacerbation of IPF in an RCT.

General Actions 
Prevent or reduce exposure to harmful environments, jobs, and medications.
Smoking cessation, additional oxygen if necessary, annual influenza and pneumococcal vaccinations, as needed

The First Line of Medicine
For some ILDs, particularly exacerbations of sarcoidosis, nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), and hypersensitivity pneumonitis, corticosteroids are most helpful.
Response rates, however, have varied between and within subtypes. Unknown are the ideal dosage and course of treatment.
– Prednisone is often started at a dose of 0.5 to 1.0 mg/kg/day for 4 to 12 weeks, with the possibility of increasing the dose based on the patient's response.
Nintedanib (Ofev), a tyrosine kinase inhibitor, decreased the incidence of FVC decline versus placebo at 52 weeks in patients with ILD related to systemic sclerosis.
In compared to placebo, nintedanib has been proven to considerably slow the annual rate of FVC reduction in patients with progressive fibrosing ILDs.
When compared to placebo over a 52-week period, two antifibrotic medications licensed for IPF showed a moderate reduction of FVC deterioration. Both lowered the mortality rates from all causes. The most conclusive relevant efficacy indicator for IPF appears to be FVC, but this is unclear.
- Pirfenidone (Esbriet) significantly improved progression-free survival relative to placebo, slowed the pace of FVC decline, and reduced respiratory-related hospitalizations in IPF patients, according to a pooled analysis of the data. Common side effects include nausea, vomiting, anorexia, weight loss, GERD, and dyspepsia, as well as rash, sleeplessness, dizziness, exhaustion, and an elevated aminotransferase. The majority of these side effects are mild to moderate and do not necessitate stopping pirfenidone.
Patients with end-stage renal disease (ESRD) or significant liver impairment should not take pirfenidone.
– It takes two weeks to titrate pirfenidone to 801 mg PO three times per day with food.
– In comparison to placebo, nintedanib decreased the annual rate of FVC decline and caused fewer acute exacerbations. The most frequent side effects include anorexia, elevated aminotransferase levels, hypertension, and GI disturbance (nausea, vomiting, diarrhea, and abdominal discomfort). It can result in birth malformations and is not advised in cases of moderate to severe liver impairment.
– Nintedanib is administered orally twice day with food in doses of 150 mg.
– Pirfenidone and nintedanib together may have a synergistic effect, however GI upset may restrict this.
There is a need for additional research.


Next Line
In individuals with ILD accompanied by polymyositis or dermatomyositis, tacrolimus added to corticosteroids (along with cyclosporine, cyclophosphamide, or no further medication) may increase event-free survival.
Several second-line medications have been used to treat Wegener granulomatosis, including: - Cyclophosphamide, which is frequently used for the condition. 1.5 to 2.0 mg/kg/day PO is administered for three to six months.
– In addition to corticosteroids, methotrexate has been used to treat mild Wegener granulomatosis. Once per week, a starting dose of 0.3 mg/kg (with a maximum dose of 15 mg) was followed by a 2.5 mg titration, with a maximum dose of 25 mg/week.
– The second-line medications mycophenolate mofetil and rituximab are among those that have been researched.

Surgical Techniques 
Lung transplantation, whether single or double, may be a final resort. The median survival after lung transplantation was found to be 4.5 years in a subset of IPF patients. Some ILDs linked to systemic illness might come back in the recipient lung.
Clinical trials to evaluate the safety and effectiveness of allogeneic human mesenchymal stem cell infusion in individuals with mild to moderate IPF are ongoing. Alveolar type II cell intratracheal transplantation may be beneficial to people with moderate to progressive IPF.

Take Action 
PFTs, 6-minute walk tests, pulse oximetry, and CXR should all be performed as follow-up examinations.


Median survival of 2.5 to 3 years is the prognosis.
Pneumothorax, cor pulmonale, pulmonary hypertension, and progressive respiratory failure are complications.

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