Treatments for IPF (Idiopathic Pulmonary Fibrosis) – 4

Idiopathic Pulmonary Fibrosis

Acute Exacerbation (AE):

– It is an unexplained worsening or development of dyspnoea within 30 days with new radiological infiltrates at HRCT abnormality often super imposed on background consistent with UIP pattern.

– The yearly incident of AE-IPF is poor, with mortality ranging from 78% to 96%.
Other causes of AEIPF such as pulmonary embolism, congestive heart failure, pneumothorax or infectin need to be excluded.

– Pulmonary infection has to be ruled out by endotracheal aspirate or BAL.

– Many patients experiencing acute deterioration require intensive care treatment, particularly when respiratory failure is associated with hemodynamic instability significant co-morbidity or severe hypoxemia.

– Mortality during hospitalization is high.

– Mechanical ventilation should be introduced only after carefully weighing the patients long-term prognosis and whenever possible, the patient’s wishes.

Prognosis:

Clinical causes of IPF are unpredictable.
– Prognosis of IPF is associated with estimated median survival time 2-5 years after diagnosis.
5 years survival for IPF ranges between 20-40 %.

– Mortality rate higher than that of a number of malignancies including colon cancer, multiple myeloma and bladder cancer.

– Recently a multidimensional index and staging system has been proposed to predict mortality in IPF.

– The name of the index is GAP and is based on gender (G) age (A), and two lung physiology variable (P) that are commonly measured in clinical practice to predict mortality in IPF.

– The highest stage of GAP (Stage III) has been found to be associated with a 39% risk of mortality at 1 year.
This model has been evaluated in IPF and other ILDs and shown good performance in predicting mortality in all main ILD subtypes.

– In addition to clinical and physiological parameters to predict how rapidly patients with IPF might progress genetic and molecular features are also associated with IPF mortality.

– It has been shown that IPF patients who have a specific genotype in the mucin MUC 58 gene polymorphism experience slower decline in FVC and significantly improved survival.

– Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on the specific genotypes is still impossible.

Epidemiology:

– IPF is the most common form of IIP.

– The prevalence of IPF has been estimated between 14 and 42.7 per 100,000 persons based on a USA analysis of health care claims date with a variation depending on the case definitions used in this analysis.

– IPF is more common in men than in women and is usually diagnosed in people over 50 years of age.
The incidence of IPF is 6.8-16.3 per 100,000 persons.

– Approximately 30,000-35,000 new patients will be diagnosed with IPH each year.

– IPF was the most common diagnosis (28%) followed by connective tissue disease – related ILD (14%), hypersensitivity pneumonitis (7%) and non-specific interstitial pneumonia (NSIP) (7%).

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Treatments for IPF (Idiopathic Pulmonary Fibrosis) – 3

Long Term Oxygen Therapy (LTOT):
In 20%, IPF guidelines ‘Oxygen Therapy’, or supplementary oxygen for home use, became a strong recommendation for use in those patients with clinically significant resting hypoxemia.

Although oxygen therapy has not been shown to improve survival in IPF some data indicate an improvement in exercise capacity.

Pulmonary Rehabilitation:
Fatigue and loss of muscular mass are common and disabling problems for patients with IPF.

Pulmonary rehabilitation may alleviate the over symptoms of IPF ad improve functional status by stabilizing and reversing the extra-pulmonary features of the disease.

Palliative Care:
It focuses on reducing symptoms and improving the comfort of patients rather than treating the disease.

This may include treatment of worsening symptoms with the use of chronic Opioids for severe dyspnea and cough.
Further oxygen therapy may be useful for palliation of dyspnea in hypoxemia patients.

Palliative care also includes relief of physical and emotional suffering and psychosocial support for patients and care givers.

With disease progression patients may experience fear, anxiety and depression.
Psychological counseling should be considered.

In selected cases of particularly severe dyspnea morphine could be considered. It reduces dyspnea, anxiety and cough.

Management and follow up:
IPF is often misdiagnosed when physiological or imagine data suggest the presence of ILD leading to delay in accessing appropriate care.

After diagnosis of IPF, and appropriate treatment choice according to symptoms and stage of diseases, a close follow-up should be applied.

Due to the high variable course of disease, the higher incidence of complications like lung cancer, a routine evaluation every 3 to 6 months, including spirometry (body plethysmography) diffusion capacity testing, chest x-ray, 6MWT, assessment of dyspnea, quality of life, oxygen requirement is mandatory.

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Treatments for IPF (Idiopathic Pulmonary Fibrosis) – 2

Pulmonary Fibrosis

Pulmonary Fibrosis

Nintedanib:
Nintedanibis an investigational orally-administered triple angiokinase inhibitor that targets receptor tyrosine.
Kinases involved in the regulations of angiogenesis -fibroblasts growth factor receptor (FGFR), platelet derived growth factor receptor (PDGFR) which have also been implicates.
Nintendanib, like Pirfenidone was approved for the treatment of IPF by the U.S. FDA in October 2014.

Future Therapeutic Options:
Many agents are investigated I Phase II clinical trials for IPF, including the ‘monoclonal antibodies’ simtuzumab tralokimob, lebrikizumab and FG-2019, a lysophoshpatidic acid receptor antagonist (BMS=986020).

A phase II study of STX-100 is also ongoing.

These molecules are directed against several growth factors and cytokines that are known to play a role in the proliferation, activation, differentiation or inappropriate survival of fibroblasts.

Non Pharmacological Interventions:

Lung Transplantation:
Lung Transplantation may be suitable for those patients, physically eligible to undergo a major transplant operation.

In IPF patients, lung transplantation reduces the risk of death by 75% as compared with patients who remain on the waiting list.

Since the introduction of the lung allocation score (LAS), which prioritizes transplant candidates based on survival for lung transplantation in the USA.

Symptomatic patients with IPF younger than 65 years of age and with a body mass index (BMI) ≤ 26kg/m² should be referred for lung transplantation, but there are no clear data to guide the precise timing for LT.

Bilateral lung transplantation is superior to single lung transplantation in patients with IPF.
Five-year survival rates after lung transplantation IPF are estimated at between 50-56%.

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Treatments for IPF (Idiopathic Pulmonary Fibrosis) – 1

Pulmonary Fibrosis

Pulmonary Fibrosis

Treatment:

The goals of treatment in IPF are essentially to reduce the symptoms, stop disease progression, prevent acute exacerbations and prolong survival. Preventive care (e.g. vaccinations) and symptom based treatment should be shared early in every patient.

Pharmacologic Interventions:

A number of treatments have been investigated in the past for IPF, including interferon gamma-1β, bosentan, ambrisentan and anticoagulants, but there are no longer considered effective treatment options.

Many of these studies were based on the hypothesis that IPF is an inflammatory disorder.

Pirfenidone:

Pirfenidone is a small molecule that combines both the anti-inflammatory, anti-oxidant, and anti-fibrotic effects in experimental models of fibrosis.
Pirfenidone marketed under the trade name ‘Esbriet’ is approved in Europe for the treatment of patients with mild-to-moderate IPF.

N-Acetylcysteine and Triple Therapy:

N-Acetylcysteine (NAC) is a precursor to glutathione, an antioxidant.
Treatment with high doses of NAC may repair an oxidant-antioxidant imbalance that occurs in the lung tissue of the patients with IPF.

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IPF : Pulmonary Function Test

Pulmonary Function Test:
Spirometry reveals a reduction in the vital capacity (VC) with a proportionate reduction in airflows or increased airflows for the observe vital capacity.

The latter findings reflects the increased lung stiffness (reduced lung compliance) associated with pulmonary fibrosis, which leads to increased lung elastic recoil.

Measurement of static lung volumes using body plethysmography or other techniques typically reveals reduced lung volumes (restrictions). This reflects the difficulty encountered in inflating the Fibrotic lungs.

The diffusing capacity for carbon monoxide (DLCO) is invariably reduced in IPF and may be only abnormality in mild or early disease.

Its impairment underlies the propensity of patients with IPF to exhibit oxygen desaturation with exercise which can also be evaluated using the 6 minutes’ walk test (6 MWT).

Terms such as mild moderate, severe are used for staging diseases and are commonly based on resting pulmonary function test ‘measurements’. There is no clear consensus regarding the staging of IPF patients and what are the best criteria and values to use.

Mild to moderate IPF has been characterized by the following functional criteria:
Forced vital capacity (FVC) of ≥ 50%
DTOC of ≥ 30%
6 MWT distance ≥ 150 meters

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Broncho-Alveolar Lavage: A diagnostic procedure in ILD

Bronchies

Bronchies

Broncho-Alveolar Lavage:

Broncho-alveolar lavage(BAL) is a well tolerated diagnostic procedure in ILD.

Broncho-alveolar lavage(BAL) cytology analysis (differential cell counts) should be
considered in the evaluation of patients with IPF at the discretion of the treating physicians:
Malignancy,
Infections,
Eosinophilic Pneumonia,
Histio-cytosis x, or
Alveolar proteinosis.

In the evaluation of patients with suspected IPF, the most important application of Broncho-alveolar lavage(BAL) is in the exclusion of other diagnosis.

Prominent lympho-cytosis allows excluding a diagnosis of IPF.

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History of IPF (Idiopathic Pulmonary Fibrosis)

In the absence of UIP pattern on HRCT a surgical lung biopsy is required for confident diagnosis.

Histologic specimens for the diagnosis of IPF must be taken at least in three different places and be large enough that the pathologist can comment on the underlying lung architecture.
Small biopsies, such as those obtained via transbronchial lung biopsy (performed during bronchoscopy) are usually not sufficient for this purpose.

Hence larger biopsies obtained surgically via a ‘Thoracotomy’ or ‘Thoracoscopy’ are usually necessary.
Lung tissue from people with IPF usually show a characteristic histopathologic UIP pattern and so is the pathologic counterpart of IPF.

Although a pathologic diagnosis of IPF, a UIP often corresponds to a clinical diagnosis of IPF, a UIP histological pattern can be seen in other diseases as well, and fibrosis of known origin (e.g. Rheumatic diseases).
There are four key features of UIP including interstitial fibrosis in a ‘patch work pattern’ interstitial scarring, honeycomb changes and fibroblast foci.

Fibroblastic foci are dense collections of fibroblasts and scar tissue and together with honeycombing, are the main pathological findings that allow a diagnosis of UIP.

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Important “Remedies” mostly used in IPF

IPF (Idiopathic Pulmonary Fibrosis) : Important remedies to get cure

Beryllium:

Beryllium is indicated for people where there is formation of granulomas/nodules those are formed in the lung and may appear in other bodily systems and organs. Beryllium has been found useful in the treatment of “Sarcoma” in Lung Cancer. It is indicated for cases when the individual has difficulty in breathing and lung pain made worse when it moves. There may be deep, dry cough and other respiratory diseases present, like Emphysema.

Silicea:

Silicea is indicated in cases of Fibroid development of the lung tissue is characteristic, wit thickening and scarring. The silicea patient is chilly, wanting to sit near the heater for warmth. Aversion to dratts, cold hands and feet, lack of appetite is seen in the patient. The remedy may helpful for relieving sharp pains in the lungs, hemorrhaging in the capillaries and coughing with thick phlegm.

Arsenicum Album :

> Better from heat, from head elevated warm drink.
> Worse, wet weather, after midnight from cold, cold drinks or food seashore right side.
> The patient is unable to lie down, he has fear of suffocation.
> The air passages are constricted in the midnight.
> In the Ars alb patient asthma is worse in midnight.
> There is burning in chest in this patient. Parkinson’s Disease(PD).
> Suffocative catarrh.
> Cough is worse after midnight, worse lying on back.
> The expectoration is scanty frothy in this patient.
> Darting pain through upper third of right lung.
> There is wheezing respiration in Are ulb patient.
> Haemoptysis with pain between shoulders is found in Ars alb patient.
> There is burning heat all over.
> Cough is dry, as from sulphur fumes, after drinking.

Causticum:

> Causticum patient feels better in Damp, wet weather warmth.
> Heat of bed is felt by the patient.
> Expectoration is day time only.
> Mucous expectoration found in afternoon.
> There is cutting pain in right side of nose.
> Running/blocked nose.
> Hoarseness with pain in the chest, aphonia.
> Cough with raw soreness of chest.
> Cough with pain in hip, especially left worse in evening.
> The patient can not lie down at night.
> Difficulty of voice of singers and public speakers.

Hepar Sulph:

> The patient loses voice and coughs when exposed to dry, cold wind,
> There is hoarseness, with loss of voice.
> Cough troublesome when walking cough is dry, hoarse.
> Cough excited whenever any part of the body gets cold or uncovered or from eating anything cold.
> Crop with loose, rattling cough, worse in morning.
> There is choking cough in Hepar Sulp patient.
> When there is suffocative attack, the patient has to rise up and bend head backwards.
> The patient is anxious, wheezing moist breathing.
> Asthma is worse in dry cold air, better in damp.
> There is palpitation of heart in Hepar Sulph patient.

Kreosotum:

> There is nosebleed during coryza.
> Offensive smell and discharge in this patient.
> Chronic catarrah of the old patient.
> The patient feels better by warmth in open air, after menstruation, cold, rest.
> Inflammation of mucous membranes of respiratory organ.

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Homeopathic Medicines for IPF (Idiopathic Pulmonary Fibrosis)

IPF

IPF

It is chronic decline in lungs function. Pulmonary Fibrosis means scarring of lung’s tissues & it is a cause of worsening dyspnoea (shortness of breathing).

The required Homeopathic medicines for IPF:-

> Arsenicum Album
> Ipecause
> Berylliam
> Natrum Sulph
> Phosphorus
> Antim Tart
> Silicea
> Cuprum Met
> Nux Vomica
> Stannum Mit
> Causticum
> Sepia
> Hepar Sulp
> Lachesis
> Kali Sulph
> Kreosote
> Arsenicum Iodatum
> Kali Bi
> Belladona
> Bryonia Alb
> Rhus Tox
> Tuberculinum

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Radiology : A Diagnosis process

radiology530

 

 

 

 

 

 

In the follow up routine of IPF patients chest x-rays are useful.

Plain chest x-rays are not diagnostic but may reveal decreased lung volumes typically with prominent reticular interstitial markings near the lung bases.

The radiological evaluation through HRCT is essential point in the diagnostic pathway in IPF.

HRCT is performed using a conventional computed axial tomographic scanner without injection of contrast agents.

Evaluation slices are very thin upto 1-2mm .

Typical HRCT of the chest of IPF demonstrates fibrotic changes in both lungs, with a predilection for the bases and periphery. According to the joint ATS/ETS/JRS/ALAT 2011 guidelines, HRCT is an essential component of the diagnostic pathway in IPF which can identify UIP by the presence of:

Reticular opacities often associated with traction bronchiectasis.

Honeycombing manifested as cluster cystic aisspaces, typically of comparable diameters (3-10mm) but occasionally large.

Usually sub-pleural and characterized by well defined walls and disposed in at least two lines.

Generally one line of cysts is not sufficient to define honeycombing.

Ground-glass opacities are common but less extensive than the reticulation.

Distribution characteristically basal and peripheral through often patchy.

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