​Kembara Xtra - Medicine - Pulmonary Fibrosis

​Kembara Xtra - Medicine - Pulmonary Fibrosis 
Interstitial lung diseases (ILDs), a group of more than 200 different lung illnesses, include pulmonary fibrosis (PF), which is characterized by inflammation, cellular proliferation, and/or fibrosis within the lung interstitium and bronchial walls.
Idiopathic PF (IPF) is the most typical form of idiopathic interstitial pneumonia, which is defined as ILD when there is no known etiology.
When all other causes have been ruled out, IPF is characterized as a type of chronic fibrosing ILD that is connected to the histologic and/or radiologic appearance of typical interstitial pneumonia (UIP).

Epidemiology The most widespread ILD is present globally (25–30% of all ILD)
 Most prevalent in men over 60 Incidence
Less common in South America and East Asia (less than 4 cases per 100,000 person-years) compared to North America and Europe (3 to 9 cases per 100,000 person-years). Prevalence
According to reports, there are somewhere from 10 and 60 cases per 100,000 people in the US.

Pathophysiology and Etiology 
The pathogenesis of IPF is best explained by the recurrent, accelerated cell senescence-induced damage to the alveolar epithelium, which results in abnormal cellular repair and the deposition of interstitial fibrosis by myofibroblasts.

Genetics It is unclear how host genetic characteristics interact with environmental factors or what impact they play.
IPF risk is enhanced by mutations in the genes responsible for maintaining telomere length.
 Gene overexpression caused by an SNP in the MUC5B promoter is linked to an increased risk of IPF.
It is unclear how MUC5B and IPF are related, though.

Family history of IPF, smoking, GERD, OSA, exposure to metal dusts (lead, brass, steel), farming, birds, hairdressing, stone cutting, contact with livestock, exposure to vegetable and animal dust, air pollution, and mold are all risk factors.

Prevention Reducing the aforementioned risk factors

Pulmonary hypertension, which affects 30-80% of IPF patients, GERD, and nonidiopathic PF may all be linked to connective tissue disorders including RA and scleroderma.

Gradual onset is the diagnosis.
Breathlessness during exertion and an ineffective cough are prevalent. Weight loss, fever, exhaustion, myalgias, and arthralgias are not common constitutional symptoms.
 Previous exposure

clinical assessment
Clubbing in the late stages, cyanosis (rare) Lung auscultation: bibasilar fine, late inspiratory crackles: "Velcro" crackles Findings indicating pulmonary hypertension and RV failure (elevated JVP, RV parasternal heave, noisy P2, LE edema) Connective tissue disorder symptoms (changes in skin/nail folds, arthritis)


The differential diagnosis of UIP based on histology includes connective tissue disease-ILD (CTD-ILD), occupational lung disease, nonspecific interstitial pneumonia, and chronic hypersensitivity pneumonitis.

Investigations in a laboratory 

Initial examinations (lab, imaging)
Most blood tests come back normal.
Radiograph of the chest
- Diminished lung volumes and reticular opacities, mainly at the bases of the lungs
- Advanced honeycombed cysts and coarse reticular pattern
Pleural anomalies (such pleural plaques and effusions) are quite rare.


Tests in the Future & Special Considerations
Chest CT scan results: When IPF is suspected, have a high-resolution CT (HRCT) scan of the chest that includes inspiratory and expiratory images with thin slices of less than 1.25 mm, as well as prone images if there are any subpleural basal alterations.
- The four patterns of HRCT used to diagnose IPF are UIP, probable UIP, indeterminate, and alternative diagnosis.
- Bilateral, primary peripheral, lower lobe reticulation, honeycombing, and traction bronchiectasis are necessary for the UIP pattern. Without the necessity for a surgical lung biopsy, the UIP pattern on HRCT can diagnose IPF.
- Probable UIP is the classification given to similar changes (as mentioned above) with traction bronchiectasis but without honeycombing.
- Upper- or mid-lung predominance, predominant consolidation, ground-glass opacities, and widespread nodules or cysts are atypical HRCT findings that raise the possibility of an ILD other than IPF.
 Connective tissue disease serologic testing to rule out nonidiopathic causes Antisynthetase antibodies, ANA, RF, anti-CCP antibodies, Scl-70, Ro, La, U1-RNP, and Jo-1, creatine kinase, myoglobin, and  Echocardiogram to evaluate pulmonary hypertension, RV function, and cardiac function 

Other/Diagnostic Procedures
Pulmonary function testing (PFT): PFTs are performed on all IPF/ILD patients who are being assessed and treated.
- Results include:
 Reduced carbon monoxide diffusion capacity (DLCO)
Reduced spirometric values: FVC and FEV1 as a result of the decreased lung capacity with preserved FEV1/FVC ratio; decreased lung volumes (TLC, RV, and FRC); Hypoxemia and respiratory alkalosis may be visible on an ABG.
Reduced distance and exertional hypoxemia at the 6-minute walk distance (6MWD) Sleep study: - Sleep disorders with lighter and more fragmented sleep, lower REM sleep, and hypoxemia during REM sleep - Sleeping is not without tachypnea.
Bronchoscopy and bronchoalveolar lavage (BAL) may be used to rule out other diseases, such as infection or cancer.
ATS/ERS does not advise routine BAL usage for IPF diagnosis.
Bronchoscopic transbronchial biopsy is not advised because of its low sensitivity and specificity for the diagnosis of IPF.  Could aid in ruling out other ILDs
Thoracoscopic biopsy may be replaced by transbronchial lung cryobiopsy, however there is currently insufficient data to support this.
 Patients whose IPF diagnosis from a CT scan is inconclusive may benefit from the use of a genetic classifier that may be applied to transbronchial biopsy samples.
Surgical lung biopsy is the gold standard for ILDs diagnosis.
A thoracoscopic lung biopsy can be considered if the clinical and imaging data taken together do not provide a definitive diagnosis.
- The most badly damaged areas should not be used for biopsy samples because they will exhibit nondiagnostic fibrosis.
- High-risk patients shouldn't have the procedure done if they have the following conditions: High oxygen needs (>2 L/min)
The pulmonary hypertension was severe.
Rapid illness development
Several studies have compared video-assisted thoracoscopic biopsy (VATS) with open thoracotomy biopsy and found that diagnostic yield is comparable but morbidity is lower with VATS.
Histopathology - Gross pathology distinct nodular pleural surface - IPF's histopathologic pattern is called UIP, and it requires dense fibrosis with architectural distortion, subpleural and basal distribution, spatial and temporal heterogeneity, fibroblastic foci, and honeycomb changes in addition to the absence of features suggestive of an alternative diagnosis.

Diagnostic techniques: The following criteria must be met in order to diagnose IPF, according to the 2018 ATS/ERS statement on the condition:  HRCT UIP pattern
 Particular combinations of histology and HRCT patterns - With the exception of alternate diagnosis findings, the UIP pattern on HRCT would be diagnostic for all histological patterns.
- With the exception of alternate diagnosis findings, the UIP pattern on histology would be diagnostic for all HRCT patterns.
- According to ATS/ERS, a multidisciplinary discussion (including pulmonologists, radiologists, pathologists, and rheumatologists) is advised for individuals suspected of having IPF in order to make a diagnosis.

Treatment options include quitting smoking, being vaccinated against pneumococcus, the flu, and SARS-CoV-2, getting pulmonary rehabilitation, and getting referred to a transplant center. If your SpO2 is below 88%, additional oxygen is strongly advised by clinical practice recommendations. When necessary, nocturnal oximetry, polysomnography, and 6-minute walk tests of oxygen saturation should also be used to guide the oxygen prescription.


Medication 
It has been established that nintedanib and pirfenidone are safe, efficient drugs for the treatment of IPF.
Both have some benefit in preventing severe respiratory events, including as acute exacerbations and hospitalization. Each treatment has been proven to delay the rate of FVC decline by around 50% over the course of 1 year in placebo-controlled, randomized studies. Meta-analyses and pooled data also point to decreased mortality.
● Each drug is thought to cost over $100,000 a year.
Initial Line
The tyrosine kinase inhibitor nintedanib targets growth factor pathways, such as VEGF, FGF, and PDGF receptors. - The most typical adverse effect is diarrhea. Additionally, there is a slight chance of bleeding, therefore patients who are taking therapeutic anticoagulation should use it with caution, if at all. Since liver damage has been recorded, liver function should be monitored.
Pirfenidone's mechanism of action includes anti-inflammatory and antifibrotic activities, which include inhibiting the production of collagen, lowering levels of TGF- and TNF-, and decreasing the proliferation of fibroblasts. Anorexia, nausea, vomiting, photosensitive rash, and altered liver function are typical adverse effects. Reflux management: - Some evidence suggested that IPF could increase with ongoing/untreated GERD. However, there have been no head-to-head comparisons and efficacy is comparable, thus it is impossible to prescribe one medication over the other. Clinical study results are not available to support routine treatment, nevertheless.
Next Line
There are no available second-line agents.
ATS/ERS treatment recommendations for IPF include the following: - Strong recommendations against the use of: Warfarin, which is an anticoagulant
Prednisone, azathioprine, and acetylcysteine (NAC) together Ambrisentan, a selective endothelin receptor antagonist
 Imatinib, a single-targeted tyrosine kinase inhibitor
- Dual endothelin receptor antagonists (macitentan, bosentan) are conditionally discouraged.
 Sildenafil, a phosphodiesterase-5 inhibitor
 Monotherapy with NAC


Concerning Referral 
Referral to a pulmonologist for treatment and diagnosis
If the patient cannot be diagnosed using ATS clinical and radiographic criteria, a referral to a thoracic surgeon is needed.
Early referral to a lung transplant institution is advised for patients whose illness is progressively getting worse.

Further Therapies 

Randomized controlled trials are being conducted to examine various experimental treatments.

Surgical Techniques 
For carefully chosen individuals, a lung transplant can increase quality of life and extend survival. Only a small percentage of IPF patients receive lung transplants.
Only 66% of lung transplant recipients live for more than three years following the operation, and only 53% live for more than five.
Primary graft malfunction, acute and chronic allograft rejection, opportunistic infections, and malignancy are typical side effects.


Healthcare Alternatives 

None of the supplementary and alternative medicines have any established benefits. 

Admission 
A patient with an acute exacerbation of IPF should be hospitalized for corticosteroid treatment.
Mechanical ventilation is a bad sign that should be avoided if at all possible.
All IPF patients should contact with a palliative care specialist.

Follow-up: Pulmonary clinic and, if possible, an ILD clinic; serial HRCT, PFT, and 6MWD monitoring; if on antifibrotic medicines, LFT monitoring.

IPF has a poor prognosis, with a median survival of 3.8 years among persons in the United States under the age of 65.

Complications 
It is defined by increasing hypoxemia, new bilateral ground-glass opacities, consolidation, or both on HRCT imaging, which are not entirely explained by volume overload or infection. Acute exacerbations of IPF occur in 10–20% of patients per year.
- Triggers: idiopathic, aspirational, drug-related, or infectious
- Treatment: The use of glucocorticoids is only weakly advised according to the published guidelines (there is no conclusive benefit based on the data) and mechanical ventilation is not advised. You might want to suggest palliative care.
Increased risk of lung cancer, VTE, and pulmonary hypertension. In the outpatient environment, supplemental oxygen should be used to treat pulmonary hypertension. A recent study of inhaled treprostinil in patients with ILD, including IPF, showed a clinical benefit, however pulmonary vasodilator treatment has generally not been effective in treating IPF. Patients with IPF who have severe pulmonary hypertension should be referred to an expert in the condition.

---