Idiopathic pulmonary fibrosis

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The idiopathic pulmonary fibrosis or idiopathic pulmonary fibrosis (IPF) is a very serious chronic disease is often fatal, which is characterized by a steady decline in lung function. The term pulmonary fibrosis stands for scarring of the lung tissue, which leads to increasing dyspnea (shortness of breath). The fibrosis usually has a poor prognosis . The term "idiopathic" is used because the cause of pulmonary fibrosis is not yet known.

IPF mostly occurs in adulthood between the ages of 50 and 70, especially in active or former smokers; Men are affected more frequently than women.

IPF belongs to a large group of about 200 lung diseases as interstitial lung diseases ( English Interstitial Lung Disease or ILD) are referred to and have an infection of the lung interstitium. The interstitium, i.e. the connective tissue between the alveoli, is mainly affected. However, these diseases often affect not only the interstitium, but also the alveoli, peripheral airways and blood vessels. The lung tissue of individuals with IPF has a characteristic histopathological pattern as usual interstitial pneumonia ( English Usual interstitial pneumonia or UIP) is referred to. UIP is the histological or detailed radiological equivalent of the IPF.

In 2011, new guidelines for diagnosis and management of IPF were published. A German version of the international guidelines from 2013 is based on an initiative by German experts under the patronage of the German Society for Pneumology and Respiratory Medicine (DGP) and on the results of a consensus conference.

A diagnosis of IPF implies ruling out other forms of interstitial pneumonia, including other idiopathic interstitial pneumonia and interstitial lung disease (ILD) related to environmental exposure, medication, or systemic disease.

classification

Classification according to ICD-10
J84.112 Idiopathic pulmonary fibrosis
ICD-10 online (WHO version 2019)

IPF belongs to a large group of more than 200 lung diseases, which are referred to as interstitial lung diseases (ILD) and are characterized by an attack on the pulmonary interstitium, i.e. the connective tissue between the alveoli. The IPF is a form of idiopathic interstitial pneumonia (IIP), which in turn is a kind of ILD, also known as diffuse parenchymal lung disease ( english Diffuse parenchymal lung disease or DPLD).

The American Thoracic Society / European Respiratory Society (ATS / ERS) classification of IIPs from 2002 was updated in 2013.

This new classification includes three main categories of IIPs: common IIPs, infrequent IIPs, and unclassifiable IIPs. The most common IIPs include chronic fibrosing IPs (including IPF and nonspecific interstitial pneumonia [NSIP]), smoke-related IPs (respiratory bronchiolitis with interstitial lung disease [RB-ILD] and desquamative interstitial pneumonia [DIP]), and acute / subacute IPs (cryptogenic organizing Pneumonia [COP] and Acute Interstitial Pneumonia [AIP]).

Known causes of ILD must be ruled out in order to diagnose IIPs. Examples of ILDs with known causes include hypersensitive pneumonitis , Langerhans cell histiocytosis , asbestosis, and collagen vascular disease. However, these diseases often affect not only the interstitium, but also the peripheral respiratory tract and blood vessels.

Epidemiology

Large-scale studies on the incidence and prevalence of IPF are lacking.

Although very rare, IPF is the most common form of IIP. Based on an analysis of US claims against health insurers, the prevalence of IPF is estimated at 14.0–42.7 cases per 100,000 population. The wide spread results from the definitions that were used in the respective cases. IPF is more common in men than women and is usually diagnosed in people over the age of 50.

The incidence of IPF is difficult to determine because uniform diagnostic criteria have only been applied inconsistently. In the 27 EU Member States, the incidence is estimated by various sources at 4.6–7.4 people per 100,000 population, suggesting that around 30,000–35,000 new patients are diagnosed with IPF each year.

A recent monocentric, retrospective observational and cohort study conducted at Aarhus University Hospital, Denmark, in patients diagnosed with ILD between 2003 and 2009 found an incidence of 4.1 per 100,000 population / year for ILD. The most common diagnosis was IPF (28%), followed by ILD related to connective tissue disease (14%), hypersensitivity pneumonitis (7%), and nonspecific interstitial pneumonia (NSIP) (7%). The incidence of IPF was 1.3 per 100,000 population / year.

Due to the uneven spread of the disease in European countries, epidemiological data should be updated using a Europe-wide ILD and IPF registry. In Germany, the academic INSIGHTS-IPF register (Investigating Significant Health Trends in IPF, study leader Prof. Jürgen Behr ) has been operated since the end of 2012 , in which over 1000 patients are documented as of February 2019. The published data show that IPF patients are sicker in the clinical routine and have a poorer quality of life than in the controlled studies, and the approaches to treatment vary widely.

Causes / Risk Factors for IPF

IPF, or idiopathic pulmonary fibrosis, is idiopathic by definition (that is, there is no known cause), but some environmental and exposure factors can increase the risk of developing IPF. Smoking is one of the key risk factors for IPF as it roughly doubles the risk of IPF.

Other environmental influences and exposure at the workplace such as B. to metal dust, wood dust, coal dust, stone dust or silicon dioxide as well as activities in the field of agriculture / animal husbandry have also been shown to increase the risk of IPF. There is evidence that viral infections may be associated with idiopathic pulmonary fibrosis and other fibrosing lung diseases.

Etiology and pathobiology

Despite intensive research, the cause of IPF remains unknown. Occurring in IPF fibrosis with cigarette smoking, environmental factors (eg. As the occupational exposure to gases, smoke, chemicals or dust), other diseases such as gastroesophageal reflux disease ( English Gastroesophageal Reflux Disease or GERD) or with genetic predisposition (familial IPF).

However, none of these factors are detectable in all IPF patients, so that they do not provide a satisfactory explanation for the disease.

It is believed that IPF is the result of an aberrant wound healing process associated with abnormal and excessive collagen deposition (fibrosis) in the pulmonary interstitium and minimal inflammation .

It is assumed that in IPF an initial or repeated injury to lung cells, the so-called alveolar epithelial cells or pneumocytes type I and type II ( English Alveolar Epithelial Cells (AECs) , which line the majority of the surface of the alveoli) , is underlying are damaged or perish, type II pneumocytes are likely to proliferate to cover the exposed basement membrane.

During a normal repair process, the hyperplastic type II pneumocytes die, while the remaining cells spread and undergo a process of differentiation into type I pneumocytes.

Under pathological conditions and in the presence of TGF-β ( English Transforming Growth Factor Beta ), fibroblasts accumulate in the damaged region and differentiate into myofibroblasts , which secrete collagen and other proteins. In the past, it was believed that inflammation was the first event to initiate scarring of lung tissue. According to the latest findings, however, the development of fibroblastic foci precedes the accumulation of inflammatory cells and the resulting deposition of collagen.

IPF pathogenesis

This pathogenetic model is indirectly supported by the clinical features of IPF, including slow onset of disease, progression over several years, relatively rare acute exacerbations, and non-response to immunosuppressive drugs. Therapies aimed at combating fibroblast activation or at the synthesis of extracellular matrix are currently in an early test phase or are being considered for further development.

Familial IPF accounts for less than 5% of all patients with IPF and cannot be differentiated clinically and histologically from sporadic IPF. Genetic associations include mutations of the surfactant proteins A1, A2, C (SFTPA1, SFTPA2B) and the mucins (MUC5B). An interesting aspect of the MUC5B variant is its detection rate, as it is found in approximately 20% of patients of Northern and Western European descent and in 19% of the Framingham Heart Study population. Mutations in human telomerase genes are also associated with familial pulmonary fibrosis, and in some patients with sporadic IPF (TERT, TERC). Recently, an X-linked mutation in a third telomerase-associated gene, dyskerin (DKC1), was described in a family with IPF.

diagnosis

A diagnosis of IPF as early as possible is a prerequisite for an earlier start of treatment and thus for a possible improvement in the long-term clinical outcome of this progressive and ultimately fatal disease. When IPF is suspected, diagnosis can be challenging; however, it has been shown that a multidisciplinary approach involving experts in the field of interstitial lung diseases from the fields of pulmonology, radiology and pathology improves the accuracy of the IPF diagnosis.

A multidisciplinary consensus statement on idiopathic interstitial pneumonia by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) from 2000 suggested various major and minor criteria for the diagnosis of IPF. In 2011, the ATS and ERS, together with the Japanese Respiratory Society (JRS) and the Latin American Thoracic Association (ALAT), published new, simplified, and updated criteria for the diagnosis and management of IPF. Today, an IPF diagnosis requires:

  • the exclusion of known causes of ILD, such as For example: domestic or workplace-related environmental factors, connective tissue diseases or drug exposure / toxicity;
  • the appearance of a typical radiological UIP pattern on HRCT.

Usually, IPF can be diagnosed by HRCT alone, which avoids a surgical lung biopsy .

In clinical practice, the recognition of the IPF may be a major challenge, since the symptoms are often similar to symptoms frequently occurring diseases such as asthma , chronic obstructive pulmonary disease ( English chronic obstructive pulmonary disease or COPD) and heart failure . The main problem clinicians face is whether the medical history , symptoms (or signs), radiographic findings, and pulmonary function tests all correspond to a diagnosis of IPF, or whether the findings are the result of some other disease process. It has long been known that ILD, caused by exposure to asbestos , drugs (e.g. chemotherapeutic agents or nitrofurantoin ), rheumatoid arthritis and scleroderma can only be differentiated from IPF with difficulty. Other differential diagnostic considerations must include interstitial lung disease associated with mixed collagenosis , advanced sarcoidosis , chronic hypersensitive pneumonitis , Langerhans cell histiocytosis, and radiation-induced fibrosis .

Clinical features

Drumstick fingers at IPF

In many patients, symptoms are evident long before the diagnosis is made. The most common clinical features of IPF include:

  • Age over 50 years
  • dry, non-productive cough on exertion
  • progressive exertional dyspnea (shortness of breath during exertion)
  • dry, inspiratory, bi-basilar Velcro-like rattle noise during auscultation with the stethoscope (an inspiratory crackling rattle in the lungs that sounds like a Velcro that is slowly pulled apart)
  • Drumstick formation, a deformation of the tips of the fingers and toes (see picture)
  • Abnormal results in the lung function test with evidence of restricted and impaired gas exchange.

These characteristics can in part be traced back to a chronic lack of oxygen in the blood. However, they can occur in many lung diseases and are therefore not specific to IPF. However, IPF should be considered in all patients with unexplained exertional dyspnea who have symptoms such as cough, bi-basilar inspiratory crackling, or drumstick fingers .

The detection of crackling rattles during pulmonary auscultation contributes to the earlier diagnosis of IPF. Fine crackling noises can be easily recognized by doctors and are characteristic of IPF.

Crackling rattles during auscultation of a patient with IPF

If bilateral crackling noises can be heard in a patient over 60 years of age during the entire inspiration, if they persist even after a few deep breaths and are detected at different times, which can be several weeks apart, then one should think about an IPF Consider HRCT, which is more sensitive than a chest x-ray . Since crackling noises are not specific to IPF, they must lead to the initiation of a careful diagnostic process.

Recognizing these symptoms requires appropriate further research to diagnose IPF.

radiology

Chest radiographs are very useful in monitoring the progression of IPF patients. Unfortunately, the conventional overview image does not lead to a definitive diagnosis, but it can show a reduced lung volume , typically with prominent reticular interstitial markings near the base of the lung.

X-ray overview of the chest in a patient with IPF. Pay attention to the small lung fields and the peripheral reticulonodular shadows.

Radiological examination using HRCT is a fundamental element of the diagnosis of IPF. An HRCT is performed with a conventional computer tomograph without injecting a contrast agent. The sectional images for evaluation are very thin (1–2 mm).

A typical chest HRCT in IPF shows fibrotic changes in both lungs, especially in the base and periphery. According to the joint ATS / ERS / JRS / ALAT guidelines of 2011, the HRCT is an essential part of the diagnostic process of the IPF, as it can identify a UIP if the following characteristics are present:

  • Reticular shadows often associated with traction bronchiectasis
  • Honeycomb pattern, characterized by accumulations of cystic air spaces, which mostly have a comparable diameter (3–10 mm), but are occasionally larger. They are usually subpleural and are characterized by well-defined walls and appearing in at least two rows. A number of cysts are not enough to be called a honeycomb pattern.
  • Frosted glass shadows are common, but less extensive than the network structure.
  • The distribution is typically basal and peripheral, but often also patchy.
High resolution computed tomography of the thorax of a patient with IPF. The main features are a peripheral, largely basal network structure with a honeycomb pattern

histology

According to the guidelines, which were updated in 2011, a surgical lung biopsy is necessary for a reliable diagnosis if the HRCT did not show a typical UIP pattern.

Histological specimens for the diagnosis of IPF must be obtained from at least three locations and be large enough for the pathologist to assess the underlying lung architecture. Small biopsies, such as those performed during a transbronchial lung biopsy (as part of a bronchoscopy), are usually not sufficient for this purpose. For this reason, larger biopsies are usually necessary, which are surgically taken as part of a thoracotomy or thoracoscopy .

Lung tissue from people with IPF usually has a characteristic histopathological UIP pattern and is thus the pathological counterpart to IPF. Although a histopathological diagnosis of UIP is often associated with a clinical diagnosis of IPF, other diseases can also show a histological pattern of UIP and fibrosis of known origin (e.g., rheumatic diseases). There are four key characteristics for UIP: interstitial patchwork fibrosis, interstitial scarring, honeycomb pattern, and fibroblastic foci.

Fibroblastic foci are dense collections of myofibroblasts and scar tissue; together with the honeycomb pattern, they represent the main pathological findings that enable a UIP diagnosis.

Microscopic image of the histopathological manifestations in common interstitial pneumonia. The high magnification (right) shows a focus of fibroblastic proliferation near a fibrosis, in which a weak, non-specific, chronic infiltrate of inflammatory cells can be seen. A typical honeycomb pattern can be seen in the subpleural space.

Bronchoalveolar lavage

The bronchoalveolar lavage (BAL) is a good diagnostic procedure to tolerierendes ILD. Carrying out BAL cytological analyzes (differential cell counts) should be at the discretion of the attending physician when investigating patients with IPF and depending on the facility-dependent availability and experience. The BAL can reveal alternative specific diagnoses: malignancies , infections , eosinophilic pneumonia , Langerhans cell histiocytosis or alveolar proteinosis. When investigating patients with suspected IPF, the BAL makes a significant contribution to ruling out other diagnoses. A conspicuous lymphocytosis (> 30%) presumably rules out a diagnosis of IPF.

Pulmonary function tests

The spirometry shows a decrease in vital capacity (VC) with either a proportional reduction in the volumes of air or increase in air volumes for each watched Vital capacity. The latter finding reflects increasing lung stiffness (decreased compliance) that is associated with pulmonary fibrosis and leads to increased lung retraction.

Measurements of static lung volumes by body plethysmography or other methods usually show reduced lung volumes (restrictive ventilation disorder). This reflects the difficulties encountered in expanding fibrotic lungs.

The diffusion capacity of the lungs for carbon monoxide ( English Diffusing Capacity for Carbon Monoxide or DL CO ) is invariably limited in IPF and can be the only abnormality in an early or mild disease stage. The restriction of the DLCO is due to IPF patients under load to an oxygen desaturation tend, as evidenced by the 6-minute walk test ( English 6-minute walk test or 6MWT) can be determined.

Terms such as "mild", "moderate" and "severe" are sometimes used to categorize the disease into stages. They are usually based on pulmonary function test measurements with breathing at rest. In IPF patients, however, there is no clear consensus on staging, nor on the criteria and values ​​that should be used. A mild to moderate IPF is characterized by the following functional criteria:

  • Forced vital capacity (FVC): ≥50%
  • DL CO : ≥30%
  • 6MWT distance ≥150 meters.

Genetic counseling in familial IPF

An estimated 10-15% of IPF patients have some form of the disease that runs in the family, hence called familial pulmonary fibrosis. Recent studies have identified gene mutations that are associated with familial pulmonary fibrosis (see above). A test for these genetic mutations is offered in selected IPF reference centers.

With genetic counseling, patients and their families receive information on the type, heredity and consequences of genetic diseases. This information can be used to make medical and personal decisions and to calculate the risk of developing a hereditary disease. In cases where pulmonary fibrosis has more than one family member, genetic counseling and testing to determine known mutations should be done. Genetic counseling after such a mutation test enables an individual interpretation of the results, i. i.e. what the results mean for the patient's health and how this affects other family members.

forecast

The clinical course of IPF can be unpredictable. The progressive IPF is associated with an estimated mean survival time of 2 to 5 years after diagnosis.

The 5-year survival rate for IPF is 20–40%; the mortality rate is thus higher than a number of malignancies, including colon cancer, multiple myeloma and bladder cancer.

Comparison of 5-year survival rates between IPF and common malignancies. Adapted from Bjoraker et al. 1998. [34]

Possible course forms and therapeutic considerations:

The majority of patients experience a slow but steady deterioration in their condition ("slow progression"). Some patients show a slow decline ("stable") while others show a rapid deterioration ("rapid progression"). A minority of patients may experience an unpredictable acute worsening (acute exacerbation), either due to a secondary complication such as pneumonia or for reasons unknown. This event can be fatal or leave patients in a significantly worse condition. The frequency of these various spontaneous processes is not known.

This model has been used for IPF and other ILDs and has performed well with regard to the prediction of mortality for all major ILD subtypes. A modified ILD-GAP index was developed for application to ILD subtypes to calculate disease-specific survival rates.

In IPF patients, the overall mortality rate is high at 5 years, but the annual rate in patients with mild to moderate lung disease is relatively low. Therefore, year-long clinical trials of IPF treatment typically measure changes in lung function (FVC) rather than survival.

In addition to clinical and physiological parameters predicting the progression of IPF, genetic and molecular properties have also been linked to IPF mortality. So could z. B. in IPF patients with a specific genotype in the mucin MUC5B gene polymorphism (see above) a slower decline in FVC and a significantly higher survival rate can be demonstrated.

While these data are interesting from a scientific point of view, the application of a prognostic model based on specific genotypes is not yet possible in clinical practice.

treatment

Treatment goals for IPF are essentially improvement of symptoms, arrest of progression, prevention of acute exacerbations, and prolongation of survival. Preventive measures (e.g. vaccinations) and symptom-oriented treatment should be initiated as early as possible for each patient.

Pharmacological treatment

A variety of treatment options for IPF have been studied in the past, including γ-interferon , endothelin receptor inhibitors ( bosentan , ambrisentan ), and anticoagulants . Because many of the previous studies were based on the assumption that IPF was an inflammatory disease, these therapies are no longer being considered as effective treatment options.

Pirfenidone

Pirfenidone is a small molecule that has shown antioxidant, anti-inflammatory, and anti-fibrotic effects in experimental fibrosis models. Pirfenidone, marketed under the name Esbriet, is approved in Europe for the treatment of patients with mild to moderate IPF. It is also approved in Japan (trade name Pirespa), South Korea, India, China, Canada, Argentina and Mexico.

Pirfenidone was approved in the European Union based on the results of three Phase III, randomized, double-blind, placebo-controlled studies, one in Japan and the other two in Europe and the United States (CAPACITY studies, PMID 21571362 ).

A review of the Cochrane Library showed that pirfenidone resulted in a significant 30% reduction in the risk of disease progression in four studies that looked at pirfenidone versus placebo in 1,155 patients. The decrease in FVC or VC was also significantly improved by pirfenidone, although a slight slowdown in FVC decrease could only be demonstrated in one of the two CAPACITY studies. Because of these inconsistent results, the US Food and Drug Administration (FDA) requested a third phase III clinical trial, ASCEND (NCT01366209, PMID 24836312 ).

This study, completed in 2014 and published in the New England Journal of Medicine, showed that pirfenidone significantly reduced the decline in lung function and the progression of IPF. [29] The data from the ASCEND study were also combined in a pre-specified analysis with data from the two CAPACITY studies, which showed that pirfenidone reduced the risk of death by almost 50% over the course of a year of treatment.

Based on these results, pirfenidone was named Breakthrough Therapy by the US Food and Drug Administration. This designation is reserved for drugs that are used to treat serious or life-threatening diseases. Preliminary clinical evidence shows that the drug represents a significant improvement over existing therapies on one or more clinically significant endpoints.

The company that developed pirfenidone, InterMune Inc., used the drug on humanitarian grounds as part of a multi-center compassionate use program (EAP) in the United States until it was approved.

N-acetylcysteine ​​and triple therapy

Acetylcysteine (NAC) is a precursor to glutathione, an antioxidant . It is believed that high-dose NAC treatment can correct an oxidant-antioxidant imbalance that occurs in the lung tissue of IPF patients. In the first clinical study with 180 patients (IFIGENIA), it was shown that NAC reduced the decrease in VC and DLCO over an observation period of 12 months when used in combination with prednisone and azathioprine .

Recently, a large randomized controlled trial (PANTHER-IPF) was conducted by the National Institutes of Health (NIH) in the United States to investigate triple therapy and NAC monotherapy in IPF patients. This study found that the combination of prednisone, azathioprine, and NAC resulted in an increased risk of hospitalization and death. The NIH then announced in 2012 that the investigation of the triple therapy in the PANTHER IPF study had been terminated early.

The study concluded that "Acetylcysteine ​​did not offer any significant advantages over placebo in maintaining FVC in patients with idiopathic pulmonary fibrosis with mild to moderate decline in lung function."

This study also assessed NAC alone, and the result for this arm was recently published in the New England Journal of Medicine. However, NAC monotherapy was shown to have no significant beneficial effects on patients with mild to moderate IPF either.

Nintedanib

Nintedanib (development code BIBF 1120) has completed a phase II study (TOMORROW) and two phase III studies (INPULSIS-1 and INPULSIS-2). Nintedanib is a triple angiokinase inhibitor for oral administration that inhibits the receptor tyrosine kinases involved in the regulation of angiogenesis: fibroblast growth factor receptors (FGFR), thrombocytic growth factor receptors (PDGFR) and vascular endothelial growth factor receptors (VEGFR) pathogenesis that also affect the pathogenesis of fibrosis and IPF are involved. In both Phase III studies, nintedanib significantly reduced the decline in lung function by approximately 50% over a year. With regard to the secondary endpoints, there was a significant increase in the time (delayed onset) to the first acute exacerbation (see above) in the group treated with nintedanib compared to the placebo group exclusively in the INPULSIS-2 study. This increase was not observed in the INPULSIS-1 study. As for pirfenidone, the application for approval of nintedanib was accepted by the FDA and an accelerated approval process ("priority review") was granted. Nintedanib was approved in the US and Europe for all stages of IPF since 2015.

Future therapeutic approaches

A number of compounds are currently being investigated in Phase II clinical trials for IPF, including the monoclonal antibodies simtuzumab, tralokimunab and lebrikizumab, as well as FG-3019, a lysophosphatidic acid receptor antagonist (BMS-986020). A phase II study of STX-100 is also ongoing. These molecules are used to combat various growth factors and cytokines that have been shown to play a role in the proliferation, activation, differentiation, or inadequate survival of fibroblasts.

Non-pharmacological treatments

Lung transplant

Lung transplants may be an option for patients who are physically able to undergo such major surgery. IPF patients who have had a lung transplant have had their risk of mortality reduced by 75% compared to patients who are still on the waiting list. Since the introduction of the Lung Allocation Score (LAS), which prioritizes transplant candidates based on their probability of survival, IPF has become the most common indication for lung transplantation in the USA.

Symptomatic patients with IPF who are younger than 65 years and have a body mass index (BMI) of ≤26 kg / m² should be scheduled for a lung transplant. However, there is no precise data that can be used to determine the best time to have a transplant. While it is still controversial, the latest data suggest that bilateral lung transplantation is more appropriate than single lung transplantation for IPF patients. The 5-year lung transplant survival rate for IPF is estimated to be 50 to 56%. Experience with the long-term prognosis of lung transplantation in IPF compared to other indications is inconsistent.

Long-term oxygen therapy (LTOT)

In the 2011 IPF guidelines, home oxygen therapy or supplemental oxygen therapy is an important recommendation for patients with clinically significant resting hypoxemia. Although there is no evidence of an increase in life expectancy through oxygen therapy, some data show that there is an improvement in exercise capacity.

Pulmonary rehabilitation

Fatigue and loss of muscle mass are common and debilitating problems for patients with IPF. Pulmonary rehabilitation can alleviate the visible symptoms of IPF by stabilizing or regressing extrapulmonary features of the disease and improving functional status.

Few studies have been published on the role of pulmonary rehabilitation in idiopathic pulmonary fibrosis, but most of these studies have found significant short-term improvements in functional exercise tolerance, quality of life, and exercise dyspnea.

Typical rehabilitation programs include physical training, diet changes, occupational therapy, information, and psychosocial counseling.

In the late stages of the disease, IPF patients tend to stop physical activity due to progressive dyspnea. If possible, the patient should be advised against it.

Palliative treatment

The palliative care focuses primarily on relieving symptoms and improving the patient's quality of life and not to the treatment of the disease. This includes ongoing therapy of worsening symptoms with opioids in the case of acute shortness of breath and coughing. Furthermore, the palliative use of oxygen therapy can be helpful for dyspnoea in hypoxemic patients.

Palliative care also includes the relief of physical and emotional suffering, as well as psychological support for patients and carers. Such care can only be provided on an individual basis and should be understood as a supplement to disease-related therapy.

As the disease progresses, patients may experience anxiety, psychological stress, and depression. Psychological support should therefore be considered. In a recent study of IDL outpatients, including IPF patients, the degree of depression, functional status (determined by the walk test), and lung function all contributed to the severity of the dyspnea.

In selected cases with particularly severe dyspnea, the administration of morphine can be considered. It can relieve dyspnea, reduce anxiety and cough without significantly lowering oxygen saturation.

Management and follow-up treatment

IPF is often misdiagnosed, at least until physiological findings and / or imaging tests suggest an ILD, thereby delaying access to appropriate treatment. Given that IPF is a disease with a median survival time of three years from diagnosis, early referral to an institution with specific expertise should be considered for any patient with suspected or previously diagnosed IDL . Due to the complex nature of differential diagnostics, a multidisciplinary discussion between pulmonologists, radiologists, and pathologists experienced in diagnosing ILD is of the utmost importance for an accurate diagnosis.

After the diagnosis of IPF and the choice of an appropriate therapy based on symptoms and stage of the disease, a comprehensive follow-up should be initiated. Due to the unpredictable course of the disease and the high rate of complications such as lung cancer (a rate of up to 25% has been reported among IPF patients), a routine examination every 3 to 6 months is necessary, including spirometry (body plethysmography ), diffusion capacity test, and chest x-ray , 6MWT, assessment of dyspnea, quality of life and oxygen demand.

Due to growing knowledge about complications and side effects that are often associated with IPF, regular clarification of accompanying diseases is necessary. Most of them, however, only reflect the usual age-related illnesses or the side effects and interactions of the drugs used.

Acute exacerbations

Acute exacerbations of IPF (AE-IPF) were defined until 2016 as: unexplained worsening or development of dyspnoea within 30 days and new radiological infiltrates in HRCT, which often overlay a background that corresponds to a UIP pattern. In 2016, an international working group defined the exacerbations as follows: Acute, clinically significant deterioration in respiratory function, which is characterized by evidence of a newly occurring, extensive alveolar anomaly. The revised diagnostic criteria are:

  • Earlier or simultaneous diagnosis of idiopathic pulmonary fibrosis (if the diagnosis of IPF has not been made beforehand, this diagnostic criterion can be met at the current diagnosis by the detection of radiological or histopathological changes, consistent with the pattern of findings of ordinary pulmonary fibrosis (UIP))
  • Acute worsening of existing dyspnea or development of dyspnea typically lasting less than 1 month
  • Computed tomography: new bilateral opaque glass shadows and / or consolidations against the background of the pattern of “common pulmonary fibrosis” (Usual Interstitial Pneumonia, UIP). If no previous computed tomography is available, the "new" restriction can be omitted.
  • Worsening cannot be fully explained by heart failure or fluid exposure.

Events that meet the definition of acute exacerbation of IPF from a clinical point of view, but do not meet all four diagnostic criteria due to a lack of computed tomography findings, should be designated as “suspected acute exacerbations”.

The annual incidence of AE-IPF in all patients is between 10 and 15%. The prognosis for AE-IPF is extremely poor with a mortality rate of 78% to 96%. Other causes of AE-IPF such as pulmonary embolism, heart failure, pneumothorax, or infections must be ruled out. Pulmonary infections must be ruled out with endotracheal aspirates or BAL. Due to the emergency status of the patents, often only part of the examinations required by AE-IPF are carried out. Therefore, in these cases, AE can only be suspected. AE and suspected AE are clinically identical and are to be regarded as equally important with regard to the prognosis and the endpoints of the clinical studies.

Many patients who are experiencing acute deterioration require intensive care. This is especially true when the respiratory failure is accompanied by hemodynamic instability, significant comorbidities, or severe hypoxemia. However, the mortality rate during hospital stays is very high. Mechanical ventilation should only be used after carefully weighing the patient's long-term prognosis and, if possible, taking into account his or her own wishes. However, current guidelines discourage the use of mechanical ventilation in patients with respiratory failure due to IPF.

Initiatives for IPF Patients: The IPF Charter

On September 30, 2014, the IPF Charter was presented in the EU Parliament. The IPF Charter is an initiative of the IPF patient organizations and doctors from different countries. With this European Patients Charter, IPF patient organizations across Europe are calling on policymakers, healthcare providers, funders / insurers and national governments to take steps to raise awareness of Idiopathic Pulmonary Fibrosis, ensure equal and improved standards of care, and provide equal access as well create a better quality of care for IPF patients at European level. More information can be found on the website.

Known IPF cases

In other species

IPF has been identified in several breeds of dogs and cats, and has been best characterized in West Highland White Terriers. Animal patients suffering from this disease share many of the same clinical characteristics as human patients, including increased exercise intolerance, increased respiratory rate, and ultimately shortness of breath. The prognosis is generally poor.

Web links

Individual evidence

  1. ↑ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj G Raghu, HR Collard, JJ Egan et al .: An official ATS / ERS / JRS / ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. In: Am J Respir Crit Care Med. , 183 (6), 2011, pp. 788-824. doi: 10.1164 / rccm.2009-040GL . PMID 21471066
  2. ↑ a b c d e f g h i j k l m n o American Thoracic Society / European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias . This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. In: Am Respir Crit Care Med. , 165 (2), January 2002, pp. 277-304, PMID 11790668 .
  3. ↑ a b EB Meltzer, PW Noble: Idiopathic pulmonary fibrosis. In: Orphanet J Rare Dis. , 3 (1), 2008, p. 8. doi: 10.1186 / 1750-1172-3-8 . PMID 18366757 . PMC 2330030 (free full text).
  4. ↑ a b c d e Pulmonary Fibrosis Foundation. Prevalence and Incidence . Pulmonaryfibrosis.org; Retrieved April 11, 2013.
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