Idiopathic pulmonary fibrosis with the picture of a usually interstitial pneumonia (ipf/uip) J84.

The UIP was first described in 1969 by Liebow and Carrington and in 1998 by Katzenstein and Myers equated to the IPF.

Idiopathic interstitial lung parenchyma disease (IIP) involving alveolar capillary membranes and consecutive pulmonary fibrosis

The IPF occupies a special position among the IIPs because there is no assured therapy for the IPF and the prognosis is very poor.

The characteristic feature of UIP is the simultaneous occurrence of inflammation, proliferation and fibrosis.

The IPF is the most common of all IIPs, accounting for about 55%. In older studies, in which no differentiation between IPF and NSIP is made yet, the share is even 91 % (KITAICHI 1990).

The prevalence of the disease is 20/100,000 and the incidence between 7-11/100,000, but increases significantly with age.

Men are affected slightly more often than women. At the time of initial diagnosis, patients are usually between 50 - 60 years old, but young men can also be affected - in rare cases.

The median survival time is 2.5 years and worsens with increasing age.

The lethality rate is between 70 - 80 %.

Mostly idiopathic, but also a genetic component is discussed, since in about 10 % a familial clustering occurs. Patients with a family history often fall ill at a younger age.

Most patients complain about complaints that have been going on for months:

• unproductive cough
• exercise-induced dyspnea
• Drum flail fingers and / or watch glass nails (at up to 50 %)
• Hypoxemia with signs of right heart strain

occasionally also:

• weight loss
• Tiredness
• Joint and muscle pain
• subfebrile temperatures

The further course is very different. Occasionally patients remain relatively stable for years and the first episode is then terminated.

Others show a slow but progressive course and in the third group the disease progresses in several acute attacks from the outset.

The trigger for these relapses / exacerbations is not known exactly. Often the relapses occur after infections or after vaccinations (flu vaccination!). Sometimes a diagnostic measure such as transbronchial biopsy, open lung biopsy, even BAL is sufficient to trigger an exacerbation.

X-ray Thorax

At the beginning of the disease mostly still inconspicuous.

In the further course of the disease, basally accentuated and pleurane-near reticular changes become apparent.

HRCT

An HRCT should definitely be performed even if the X-ray image already shows changes.

In the basal and middle sections with subpleural accentuation a reticular pattern with a more or less pronounced honeycombing can be found.

Consolidations and nodular changes are absent, milk glass opacities mostly too, at least these are not typical for IPF.

Secondary emphysema of not inconsiderable extent is often found. Traction causes bronchiectasis and bronchiolectasis.

The mediastinal lymph nodes are often enlarged, but rarely > 2 cm.

In cases of pronounced alveolitis other differential diagnoses should always be considered.

In principle, the indication for tissue removal of any kind - even for BAL - should be narrowly defined for IPF/UIP, as these measures can trigger an acute flare of disease, which may be terminating. This is not described for the other subgroups of the IIPs.

If a biopsy should nevertheless be necessary, e.g. if the diagnosis is unclear, the BAL shows an increased cell count of neutrophil granulocytes and, to a lesser extent, an increase in eosinophils and lymphocytes.

The cell count of neutrophils allows certain conclusions about the prognosis, the higher the cell count, the worse the prognosis.

If the increase in eosinophils is more than 15% and / or that of lymphocytes more than 30%, IPF is also rather unlikely. In this case differential diagnoses should be considered.

In case of detection of distinct milk glass opacities in HRCT, it is recommended to flush this region with BAL. In such a case, the differential diagnosis would be to exclude RB-ILD, COP, DIP, EAA or NSIP.

Typical for UIP is the picture of a heterogeneously pronounced fibrosis with fibrosis esters, which are not found in all other idiopathic interstitial pneumonia.

Both in the case of rapid progression and in acute attacks, the histological picture of diffuse alveolar damage (DAD) can be found.

In IPF, UIP is always present histologically. But not every UIP histology is an IPF!

The diagnosis of an IPF can be made on the basis of main and secondary criteria.

The main criteria are:

• other known causes are excluded
• restricted gas exchange, restrictive ventilation disturbance
• in HRCT, basal reticular pattern on both sides with at most slight milky glass opacity
• no indication of possible other causes

The secondary criteria are:

• Age > 50 years
• slow-moving exercise-induced dyspnea for which there is no other explanation
• Duration of the illness is more than 4 months
• dry crackling rattling accentuated on both sides

Of the primary criteria, all 4 must be met, and of the secondary criteria, 3 of 4, in order to make a diagnosis of IPF.

Auscultation

In almost every patient bilateral sclerosiphonia can be auscultated.

Lung function

The whole body plethysmography can be inconspicuous at the beginning. In the further course of the disease, a moderate restrictive ventilation disorder with a reduction of the total lung capacity as well as the inspiratory vital capacity becomes evident.

A diffusion disturbance by measuring the CO diffusion capacity is already found in the early stages, even before the restriction occurs.

The changes mentioned above result in hypoxaemia, which the patient tries to compensate for by hyperventilation (hypercapnia).

• UIP pattern in another disease
• other forms of interstitial pneumonia (especially COP, RB-ILD, DIP, NSIP)
• Collagenoses
• Asbestosis
• Sarcoidosis

Currently, no therapy is known that could prolong survival. The most important measure is therefore the rapid detection of the disease and listing for lung transplantation.

Listing should be carried out at the latest when the disease is progressive, both clinically and in terms of lung function. This is the case if, within a period of 3 months:

• vital capacity and total lung capacity decrease by >10
• DLCO falls by >15
• Oxygen saturation drops > as 4

Previously, therapies were carried out with a combination of prednisolone and azathioprine or cyclophosphamide. However, it has now been shown that these therapeutic measures have no clear effect on the disease process.

According to the IFIGENIA study, only the combination of prednisolone, azathioprine plus an additional 3 x 600 mg ACC showed a slower deterioration of VC and DLCO. It is therefore recommended to try this medication in patients < 70 years of age and without contraindications.

Prednisolone: Initial dose 1 mg/kg bw/d, but not more than 50 mg/d. After 4 weeks halve the dose, after another 4 weeks halve it again. After another 4 weeks the further procedure should be decided individually.

Azathioprine: 2 mg/kg bw/d, but not more than 150 mg/d. The dose should be increased in 50 mg steps weekly until the target dose is reached.

ACC: 3 x 600 mg/d. In case of intolerable side effects among glucocorticoids and in elderly people ACC may be prescribed as the sole medication. A worsening of the course of the disease was not observed among them.

Oxygenation: In hypoxemia the patient should receive oxygen, but only up to a dose at which the shortness of breath has subjectively improved. There is evidence that high oxygen delivery via radical formation accelerates the progression of pulmonary fibrosis.

Morphines: If massive dyspnea at rest occurs in the final stage, morphines in higher doses should be used additionally for symptomatic treatment.

Ventilation: Hypercapnia occurs relatively late in patients with IPF as opposed to those with COPD. In cases where hypercapnia is observed early, COPD has usually already existed before.

In this clinical picture, the ventilation of the patients is a purely palliative measure, the only exception being bridging measures until transplantation. In any case, a form of non-invasive ventilation should be chosen. Invasive ventilation would require ventilation at a very high frequency and with a low volume, as the lung has a considerable stiffness and volume reduction at this stage. The only exception to invasive ventilation could be infection-related exacerbation in an otherwise early stage of IPF.

Complete remissions are not possible. The median survival is 2.5 years and worsens with increasing age.

The lethality rate is between 70 - 80 %.

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