INTRODUCTION:

Idiopathic pulmonary fibrosis (IPF) is defined as it is a chronic disease that is characterized by formation of cicatricial tissue (fibrosis) in the lungs which causes inadequate supply of oxygen into the bloodstream. The Idiopathic pulmonary fibrosis is also known as Cryptogenic fibrosing alveolitis (CFA).^1,3

Idiopathic pulmonary fibrosis (IPF) comes under the family of lung disorders called interstitial lung diseases (ILD) or diffuse parenchymal lung diseases (DPLD). IPF comes under the subgroup called as Idiopathic interstitial pneumonia (IIP). Idiopathic interstitial pneumonia (IIP) can be classified into two categories: specific clinical features and pathological patterns.³

a) Specific Clinical Features:

· Idiopathic pulmonary fibrosis

· Desquamative interstitial pneumonia – respiratory bronchiolitis interstitial lung disease

· Acute interstitial pneumonia

· Non – specific interstitial pneumonia

· Cryptogenic organizing pneumonia – bronchiolitis obliterans organizing pneumonia

b) Pathological patterns:

· Usual interstitial pneumonia

· Desquamative interstitial pneumonia – respiratory bronchiolitis interstitial lung disease

· Diffuse alveolar damage

· Non – specific interstitial pneumonia

· Organizing pneumonia, peribronchiolar inflammation.¹

Idiopathic Pulmonary Fibrosis (IPF) is correlated with the histopathologic or radiologic pattern of usual interstitial pneumonia (UIP). The cause of IPF is unknown. In case of IPF tiny air sacs called alveoli in the lungs are thicken and stiffen, causing fibrosis. IPF is occurs in aged people. People more than 50 – 70 year’s old are more commonly affected by the IPF. Men’s are more affected than the females. But nowadays females are also suffering from this disease. IPF is commonly seen in smokers as well as non-smokers.^1,3,4

The diagnosis of IPF is difficult because the signs and symptoms of IPF are similar to the other heart or lung diseases. The person with chronic obstructive pulmonary disease (COPD) and asthma also have the problem of shortness of breath. The symptoms is shortness of breath, chronic dry cough, finger clubbing, fatigue, weakness, weight loss.^1,3,4

EPIDEMIOLOGY:

Incidence and Prevalence:

IPF is the most common type of interstitial lung disease (ILD). The incidence and prevalence of IPF are not established accurately because in older reports there is variations in study methodology and absence of uniform definitions and diagnostic criteria. Depending on the method of data collection and diagnostic case definition reported incidence rates for IPF vary considerably. The rise in an IPF incident is suggested by the evidence. Since in 1944, Hamman and Rich gave the pathological description of interstitial pneumonia, several situations that now we recognize the separate disease entities for example nonspecific interstitial pneumonia and desquamative interstitial pneumonia were combined in with IPF Or it’s other name such as Cryptogenic fibrosing alveolitis.^2,4,6

It is rare condition. As compared to brain, stomach and testicular cancer it occurred frequently. As time passes the incidence has been raised. In Europe and North America 2.8 and 18 cases per 100 000 persons to be estimated. On worldwide changes there is limited data are available. But in Asia and South America may be there is less incidences ranges from 0.5 to 4.2 per 100 000 per year to be estimated.^2,4,6

Mortality of IPF:

The mortality rate is higher in men than women and it is increased with the age. An increase in the IPF related mortality was shown by the recent mortality data from US. The mortality rate from 40.2 deaths per 1,000,000 in 1992 to 61.9 deaths per 1,000,000 in 2003 was increased in men and from 39.0 deaths per 1,000,000 in 1992 to 55.1 deaths per 1,000,000 in 2003 in women.⁴

Risk factors:

There are several risk factors for developing the disease such as:

a) Extrinsic factors:

1. Cigarette smoking:

Smoking is correlated with the IPF. The cigarette smoke exposure means the multiple effects in the lungs which are correlated with the development of IPF. Alveolar epithelial cells which are correlated with the epithelial-to-mesenchymal transition are in contact of cigarette smoke in vitro overexpress genes and take a fibroblast-like phenotype. The important mediator of fibrosis in IPF is nicotine which itself can spur the production of TGF-β.^4,9

2. Environmental exposures:

Some environmental and occupational factors are also linked with the IPF. Some are metal, wood dust, farming, poultry, stone cutting or polishing, sand, domestic waste etc are associated with the IPF.^4,9

b) Intrinsic factors:

1. Genetic factors:

The first clue regarding genetic susceptibility to IPF was provided by the study of familial grouping of pulmonary fibrosis. Alveolar stability is affected by some genes which encodes surfactant protein A and C – SFTPC, SFTPA1, SFTPA2; this genes affects cell senescence by disrupting telomerase function which includes TERT, TERC also DKC1, PARN, RTEL1; this genes affects host defence which involves Human airway mucin MUC5B and immune regulator TOLLIP and this genes also impair integrity of epithelial barrier and also encodes mutant desmosomal protein.^4,9

Multiple loci associated with risk for IPF was identified from the studies of two genome-wide association. While most of them are rare, from the study of GWAS is found that the variant of MUC5B and TOLLIP are common. In control subjects, the minor allele is related with the MUC5B higher expression in lung tissue, whereas the level of MUC5B are uniformly increased by neglecting the genotype in established IPF. While for developing IPF MUC5B minor allele has been made on the risk of approximately 30%, but in established IPF as compared with wild-type genotype it is related with better survival. Similarly, minor allele of TOLLIP is protective against the IPF development, it is related with the poor survival in established IPF.^4,9

2. Aging:

IPF is most commonly diagnosed in older people. On both the organismal and cellular levels the senescence are of relevance. An elevated incidence and prevalence of IPF with older age has indicated by the population studies. In majority of cases the diagnosis of IPF was done in the fifth to seventh decades of life.⁹

3. Male sex:

Across the world, IPF is more common in men than women. In the bleomycin mouse model of pulmonary fibrosis, sex hormones has been considered as one of rationale for sex differences. The animal model suggest that the female sex harmones are protective against the pulmonary fibrosis while male sex harmones are related with the pulmonary fibrosis. The sex harmones effect is organ and species specific, though, to determine their role in IPF it is necessary to study sex harmones in human samples.⁹

4. Gastroesophageal reflux (GER):

Several studies reported that the quantity of GER is high in patients with IPF. Up to 90% of abnormal GER is present in IPF patients. Acid aspiration into the lung can induce the pulmonary abnormalities are suggested by the animal studies. Still, the exact relation between the chronic microaspiration and IPF remains unspecified.^{[4, 9]}

5. Obstructive sleep apnea (OSA):

In IPF cases obstructive sleep apnea is common. OSA is caused due to partially or completely collision of upper airway and it is characterized by the periodic apnea or hypopneas.⁹

6. Diabetes mellitus:

Several research established the relation between diabetes mellitus and IPF. It is systemic disease causes damages to the kidney, nerves and cardiovascular systems.⁹

7. Herpesvirus infection:

This virus is common in IPF is found from the evaluation of lung tissue and serum from IPF patient. The different herpesvirus are : Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-7 (HHV-7), and human herpesvirus-8 (HHV-8). As compared to 35% of controls the 97% of IPF patient are tested positive for at least one of the above viruses.⁹

8. Lung microbiome:

In the development and progression of IPF the role of constituent micro-organism has been recently investigated. Microbes serves as a stimulus for microinjury within the current prototype of IPF pathogenesis. In a prospective study, Molyneaux, et al announced that as compared to controls and moderate COPD patients the IPF patients had more bacterial burden in bronchoalveolar lavage (BAL) fluid.⁹

Clinical descriptions:

History and physical:

In IPF upon exertion patients experiences breathlessnes. In daily activities they are bothered by a dry cough. In IPF symptoms such as weight loss, fever and arthralgias are unusual.³

Diagnostic laboratory findings:

In IPF there is no specific laboratory abnormalities. Nevertheless, mild increase of the erythrocyte sedimentation rate, seen a low-positive titer of anti-nuclear antibody (ANA) or low positive rheumatoid factor and a general state of inflammation are thought to represent. Blood count may reveals polycythemias in advanced diseases.³

Physiologic changes:

Decreased measures of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) is revealed by routine spirometry. In IPF ratio of forced vital capacity to forced expiratory volume in one second is remains normal or increased consistent with restrictive physiology. Measurement of the diffusion capacity demonstrate that the gas exchange is impaired in IPF.^3,4

Natural history and prognosis:

The IPF natural history is completely unknown. New perception into the IPF natural history has been obtained from the secondary analysis of the placebo groups gathered for recent multi center clinical trials.³

Acute exacerbations of IPF:

The “acute exacerbations” is the phenomenon in which in the IPF patients Japanese physicians were firstly described the acute, unexpected deterioration. Also known as the “terminal complication” of IPF. The pathological findings of acute exacerbation as diffuse alveolar damage (DAD) superimposed on UIP was first reported by the COLBY and KITAICHI, in the English medical literature.^3,15

Pulmonary hypertension and IPF:

The reported that the pulmonary hypertension can be occurred in 32% to 84% of IPF patients. Because of the triggers for the evaluation of pulmonary pressures the exact prevalence is not cleared. In IPF best pulmonary hypertension detection method remains unsettled.³

IPF and emphysema:

A syndrome is described by several groups in which IPF is accompanied with pulmonary emphysema. A strong determinant of secondary pulmonary hypertension is a combination of IPF and emphysema. On measures of physiologic function, exercise capacity and prognosis the combined IPF and emphysema has major effects.^3,4

Lung cancer and IPF:

On the basis of two reasons, IPF was thought to be correlated with increased risk of lung cancer. Firstly, In IPF patients the lung cancer was found simultaneously was showed by the autopsy studies. Secondly, during the follow-up of IPF there were several epidemiological reports of increased incidence of lung cancer.^3,14

Pathogenesis:

The characteristic histopathological hallmark of IPF is usual interstitial pneumonia (UIP). Features involves temporal and spatially heterogeneous fibrosis, clusters of fibroblasts and myofibroblasts (fibroblastic foci) and excessive deposition of disorganised collagen and extracellular matrix (ECM), with resulting the normal lung architecture distortion, with or without honeycomb cyst formation. While mechanism of pathogenesis are incompletely unknown, the recently accepted prototype suggest that the injury to the alveolar epithelium is succeeded by the burst of pro – inflammatory and fibroproliferative mediators that invoke responses correlated with normal tissue repair.^3,5

The pathogenic concepts are given below:

1. Initiation:

a) Genetic basis for IPF:

An abundance of evidence to support a genetic predisposition to pulmonary fibrosis are provided by the studies of familial interstitial pneumonia and large-scale genome-wide association studies (GWAS).⁵

b) Surfactant protein related genes:

The alveolar epithelial type II cell (AEC type II) – specific protein is a surfactant protein and considered as an essential for normal lung function and homeostasis. In the rare cases of sporadic IPF, the surfactant protein variants C (SP – C) and A2 (SP – A2) have been implicated in the development of familial pulmonary fibrosis (FPF). Studies suggest that within the endoplasmic reticulum (ER) these mutations prevent the correct folding of proteins, leading to the ER stress and starting of the unfolded protein response (UPR). A series of protective biochemical pathways are represented by UPR and that aim is to match the protein capacity of ER. Interestingly, within the alveolar epithelial type II cells of IPF patients the UPR activation markers are also increased, while the exact mechanistic drivers remains mostly unexplained.⁵

c) UC5B Promoter Polymorphism:

For the familial and sporadic idiopathic interstitial pneumonias development the MUC5B promoter single-nucleotide polymorphism (SNP) has been identified as a strong risk factor. For the minor allele of these MUC5B polymorphism odds ratios for disease in subjects heterozygous (GT) and homozygous (TT) have been quoted for familial as 6.8 (95% confidence interval (CI), 3.9–12.0) and 20.8 (95% CI, 3.8–113.7) and for IPF 21.8 (95% CI, 5.1–93.5).In the pathogenesis of IPF the role of this gene has been fully unexplained, while mechanistic studies proposed that overexpression or MUC5B, driven by the promoter polymorphism, increases chronic mucus hypersecretion, impairs mucociliary clearance in the broncho-alveolar region, potentiates chronic inflammation and injury.⁵

d) Other gene variants:

Genome-wide association studies (GWAS) in association with the development of IPF identified the three single nucleotide polymorphisms (SNPs) in the toll- interacting protein (TOLLIP) gene. However minor allele G for reference SNP 5743890 (rs5743890) protect against the IPF development and it is with established diseases associated with increased mortality in patient of IPF.⁵

e) Telomeres:

The repeating of both 5′-TTAGGG-3′ DNA units and associated binding proteins (the shelterin complex) are the telomeres specialised loop structures which includes tips of chromosomes, protecting from degradation to chromosomal DNA. During each cycle of DNA replication progressive shortening of telomeres occurs till a critical telomere length is reached, triggering cell senescence or chromosomal degradation and cell death. The enzyme telomerase consists protein (hTERT) and RNA (hTR) subunits that during DNA replication add 5′-TTAGGG-3′ repeats to the tips of chromosomes. It is very low or absent in normal somatic cells but active in germline and stem cells. With premature ageing and abnormal tissue repair Accelerated telomere shortening has been associated.⁵

Six telomere-related genes have been associated with familial pulmonary fibrosis (FPF) such as Telomerase reverse transcriptase (TERT), Telomerase RNA component (TERC), Dyskerin pseudouridine synthase 1(DKC1), TRF1 (Telomerase repeat factor 1) interacting nuclear factor 2 (TINF 2), Regulator of telomere elongation helicase 1(RTEL1) and Poly(A) specific ribonuclease (PARN). The function of these genes: TERT, TERC, DKC1, TINF2, RTEL1 and PARN are encodes the telomerase protein subunit (hTERT), encodes the telomerase RNA subunit (hTR), active role in telomerase stabilization, provides instructions of making part of the shelterin protein complex, encodes DNA helicase that helps stabilize telomeres during RNA replication and involved in TERC RNA maturation respectively. In those with telomere-related gene mutations the idiopathic interstitial pneumonias cases of unknown cause (nonspecific interstitial pneumonia, desquamative interstitial pneumonia, pleuroparenchymal fibroelastosis, and IPF) as well as ILD attributed to known causes (chronic hypersensitivity pneumonitis and connective tissue disease-associated ILD) have been identified.⁵

2. Environmental factors:

Epidemiological studies have highlighted the factors such as occupational and environmental exposures to wood and metal dust, pollution, gastric aspirations, smoking and infection due to that increased the risk of developing IPF. CS is the most common environmental exposure associated with the IPF development. Studies have shown that in the pathogenesis of IPF CS increases methylation of specific gene promoters involved such as WNT7A and changes the methylation of DNA, modification of histone and micro-RNA expression. In the initiation of IPF viral pathogens have also been involved.⁵

3. Propagation:

In the propagation of IPF a significant juncture is the inability of the dysfunctional epithelium to regenerate following repetitive injury. When epithelium is damaged the basement membrane are disrupt and thus barrier to the alveolar capillary. In the interstitial and alveolar spaces capillary leakage of protein occurs, as the part of the ongoing attempted repair process the activation of the coagulation cascade and the remodelling of abnormal vascular.⁵

The process by which phenotypic characteristics of mesenchymal cells are acquired by epithelial cells, a process in which requiring transcriptional machinery and cellular reprogramming changes are called the Epithelial-mesenchymal transition (EMT). While in embryological tissue an EMT is a physiological phenomenon, in normal wound healing it is a rare event and in response to sustained inflammation and injury occurs. In the initiation of this process involved transforming growth factor β1 (TGF β) are thought to be a key cytokine. While there is evidence indicates that in IPF the epithelial cells acquire some features of mesenchymal, the formal EMT with transition of AEC to fibroblasts occurred or not is remains uncleared, because there are no definitive specific fibroblast cell markers. In animal model exogenous administration of epithelial cell mitogens/motogens appears to be capable to attenuate fibrosis. Myofibroblasts secreted the one of these growth factors such as hepatocyte growth factor (HGF) and function is to oppose those of TGF-β1. The another epithelial cell mitogen/motogen is keratinocyte growth factor (KGF) which is secreted by mesenchymal cells.^5,7,8

In human IPF upregulation of Fas signaling pathway has been demonstrated and sometimes with conflicting results, in epithelial cell apoptosis the role of Fas-Fas ligand cascade has explored by the studies in animal model. In the pathogenesis of IPF angiotensin II has been proposed as a soluble mediator of epithelial cell apoptosis. To block Fas-mediated epithelial cell apoptosis the inhibition of angiotensin II or the angiotensin receptor has been shown. Through generation of angiotensin II paracrine epithelial cell apoptosis can be induced by the IPF-derived fibroblasts.⁷

Diagnosis:

IPF patients are present with the exertional dyspnea and nonproductive cough. In the fifth and sixth decades the disorders are present and it is more common in men than women. Before diagnosis patients are evaluated and treated for other diseases such as bronchitis, heart failure and asthma. Symptoms like low-grade fever and myalgia may be shown but are not common. In most patients the physical examination discloses the fine bibasilar inspiratory crackles i.e. Velcro rales. In the 50% of patients clubbing is seen. The collagen vascular diseases such as inflammatory arthritis, rashes or myositis findings the suggest an alternative diagnosis.^1,2

The laboratory abnormalities are mild and nonspecific in which in up to 30% of patients observed that the in markers of inflammation such as erythrocyte sedimentation rate Or C-reactive protein level increased in mild anemia and in rheumatoid factors or anti-nuclear antibodies increased in nonspecific anemia. The presence of autoantibodies does not imply an underlying collagen vascular disorder in the absence of other findings of a system ailments. Due to decreased lung compliance a parenchymal restrictive ventilatory defect, with reduction in total lung capacity, functional residual capacity and residual volume are revealed by the pulmonary function tests. However, a concurrent obstructive ventilatory defect is shown in patients who are smoked. By decrease in the carbon monoxide diffusing capacity or by hypoxemia with graded exercise testing demonstrated that the impairments in gas exchange.¹

The bilateral reticular opacities are revealed in idiopathic pulmonary fibrosis by typical chest radiographs. The reason for cystic dilatation of the distal air spaces is the progressive fibrosis and is detected as peripheral “honeycomb”. The reason of traction bronchiectasis is the decreased parenchymal compliance and is detected as thickened and dilated airways. Normal radiographic studies reported that all patients will have an abnormal chest radiograph on presentation, unusual cases of biopsy-proved idiopathic pulmonary fibrosis. An alternative diagnosis or superimposed complicating illness is strongly suggested by the presence of pleural effusions, air bronchograms, confluent shadows or hilar adenopathy.^1,8

In the initial evaluation of patients with suspected IPF the high-resolution CT scan of the chest has central role. For a pattern of usual interstitial pneumonia in the 2011 international high-resolution CT criteria defines three diagnostic categories such as usual interstitial pneumonia, possible usual interstitial pneumonia, and inconsistent with usual interstitial pneumonia. Without features considered incompatible for diagnosis of usual interstitial pneumonia with a diagnosis of IPF the high-resolution CT criteria include the presence of honeycombing in a basal and subpleural distribution. The ability of physicians expert was examined by a study to identify correctly high-resolution CT scans in the diagnosis of interstitial lung diseases from patients with biopsy-proved idiopathic pulmonary fibrosis. In many patients without need of biopsy the experienced clinicians can make a confident diagnosis of IPF. For diagnosis a lung biopsy is needed when the studies of diagnosis do not support a confident diagnosis of IPF or when the low experienced clinicians are there.^1,16

For identifying the specific IIP lung biopsy remains the important. A strong predictor of outcome at the time of diagnosis in patients with idiopathic pulmonary fibrosis is the diagnosis made by the surgical lung biopsy of usual interstitial pneumonia pattern. A large piece of lung parenchyma is required because the diagnosis depends on grading lesions that vary in both the age and location. Hence, to rule out other disorders that minimize the IPF used the transbronchial biopsies. By using some techniques such as thoracotomy, less invasive video-assisted or thoracoscopic technique surgical lung biopsy can be performed. To specific abnormal regions of the lungs preoperative high-resolution CT scans direct the surgeon. From several sites biopsies are required for optimal evaluations. The patients which undergo ventilation this procedure can be performed safely in that patients, but it may be correlated with the substantial complications such as prolonged bronchopleural fistulas and post-thoracotomy pain.^1,16

To study patients with IPF used the other techniques such as gallium lung scanning and bronchoalveolar lavage.¹

Pharmacological treatment:

Pirfenidone –

For the treatment of IPF the first drug to be licensed specifically is pirfenidone. In experimental models of pulmonary fibrosis pirfenidone has combined effects including anti-inflammatory, antioxidant and anti-fibrotic. The promising agent with therapeutic potential is the pirfenidone. Oral dose of pirfenidone is also available. Pirfenidone, in vivo in animal models experimentally induced pulmonary fibrosis attenuated and reduces the growth factor-driven fibroblast proliferation or in vitro production of extracellular matrix. For IPF in 2005 in Japan first RCT of pirfenidone was completed. By Shionogi and Co for oral use 200 mg tablet of pirfenidone and matching placebo were provided.^{4, 11,17}

Nintedanib –

The intracellular inhibitor which target the multiple tyrosine kinases is a Nintedanib. Nintedanib is also known as BIBF 1120. In the last decades for IPF there has been an exponential increase in the number of compounds entering clinical trials. Nintednib is the derivative of oxindole. By using various growth factor receptors such as platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptors (VEGFR) 1 and 2, and fibroblast growth factor receptors (FGFR) 1, 2 and 3 nintedanib suppresses signals. Originally, for use in indications of oncology nintedanib developed as a angiogenesis inhibitors. Nintedanib, in vitro in lung fibroblast of human and in vivo in bleomycin-induced pulmonary fibrosis in rodent model proved that have the anti-fibrotic activities. In patients with IPF decreased the lung-function decline and acute exacerbation with the treatment of 150mg nintedanib twice daily was suggested by the phase 2 trials.^4,10,11,12

N-acetyl-cysteine (NAC):

The precursor of the glutathione which is a free radical scavenger and endogenous antioxidant in lung is the N-acetyl-cysteine (NAC). The important in IPF pathogenesis is the oxidative stress-mediated injury of alveolar epithelial cells. In the lungs of patients with IPF reduced the level of glutathione. In IPF the level of glutathione is increased due to the administration of NAC orally that is demonstrated by the small pilot studies. For the Idiopathic Pulmonary Fibrosis International Group Exploring N-acetyl-cysteine I Annual (IFIGENIA) trials paved the way because of the above observations.^{4, 17}

Non-pharmacological treatments:

Lung transplantation:

Patients undergoing transplantation for IPF was worsened than patients undergoing transplantation for some other indication when it is matched depending upon multiple variables For this difference the reason are not cleared. The most beneficial approach remains a matter of controversy was represented by the single or double lung transplantation. Bilateral lung transplantation is correlated with the longer survival, while the patient which undergo unilateral transplantation in that patient the more common cause of death is cancer.^{4, 18}

Pulmonary rehabilitation (PR):

In IPF patients for decreasing symptoms and improving exercise tolerance, functional capacity and scores of dyspnoea the pulmonary rehabilitation has been proven effective. The anxiety and depression symptoms may improved by pulmonary rehabilitation. In IPF patients with significant improvement in 6-minute walk test and quality of life the pulmonary rehabilitation has been associated. Behavioural changes including weight loss, pacing and energy conservation strategies also adoption of specific breathing and specific patterns involved in successful pulmonary rehabilitation. Patients with IPF take an advantage from the home-based pulmonary rehabilitation.^4,13

Palliative care:

In advanced disease, on physical activities and quality of life the dyspnoea may affected. Without significant minimization in oxygen saturation the low dose of diamorphine decreases the dyspnoea, anxiety and cough it is reported by the Allen and colleagues. Fear, anxiety and depression were experienced in patients with disease progression and therefore psychological counselling and pharmacological treatment should be needed. The aim to improve the symptoms like fear, anxiety, depression in IPF patients by palliative and supportive intervention with pharmacological and nonpharmacological intervention.^4,13

Cough:

In patients with IPF troublesome symptoms such as cough adversely affects on quality of life. In patient with IPF to control cough anti-acid treatment did not help was showed by a recent-controlled-trials. Conventional antitussive agents include opiate-derived preparations are often of limited benefit in the later stages of the condition, in IPF patients treatment of cough remains problematic. To capsaicin cough sensitivity was found by the one small, uncontrolled, open labelled study and after one month of high dose of oral corticosteroids decreases the cough symptoms score and when decreased the steroid dosage cough was recurred. On cough and quality of life a beneficial effect of thalidomide was demonstrated by a recent double-blind trial by comparing thalidomide with placebo. In IPF patients side effects of thalidomide was limit its long-term uses. The side effects such as constipation, bradycardia, dizziness and peripheral neuropathy. In more than 80% of patients with IPF cough is present. And in IPF patients cough is an independent predictor of progression.^4,13

CONCLUSION:

Idiopathic pulmonary fibrosis is a fatal fibrotic lung disease with unknown cause and characterized by the histological pattern of usual interstitial pneumonia. The diagnosis, treatment and management of patients with IPF is found to be challenging. So there is need of consensus for defining diagnostic criteria of IPF there are many ongoing studies that describes inadequately characterized patient population. So we just recommend that in future this idiopathic pulmonary fibrosis term is only used in reference to patients with known or suspected UIP histology. In this case the treatment is just remain unsatisfactory for patients with UIP. So there is need of randomized and controlled treatment trials.

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Received on 17.08.2021 Modified on 10.10.2021

Asian J. Res. Pharm. Sci. 2022; 12(1):42-48.

DOI: 10.52711/2231-5659.2022.00008