Acute exacerbations of fibrosing interstitial lung diseases: clinical features, prognosis and associations of inflammatory cells with disease course.

Pulmonary fibroses are a large group of different types of interstitial lung diseases, in which peripheral lung tissue is replaced by scar tissue. The most common type of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF), the cause of which is still unknown. In IPF, incurable lung dysfunction is developed as a result of scarring. The disease course can also be progressive and irreversible in other types of pulmonary fibrosis than IPF. Pulmonary fibrosis is the most common cause of lung transplantation in Finland and worldwide.

10−30% of patients with progressive pulmonary fibrosis experience an acute exacerbation, in which new alteration is present in addition to principal change related to pulmonary fibrosis. The condition is associated with rapidly progressive respiratory failure and high mortality. An acute exacerbation can occur at any stage of the disease, making the prognostic assessment of pulmonary fibrosis challenging. The cause of acute exacerbation is still unknown, although some predisposing factors such as lower respiratory tract infections and lung medical procedures have been identified. Our study revealed that acute exacerbation of IPF was associated with shorter survival than acute exacerbation in other type of pulmonary fibrosis. In addition, we found out that several inflammatory cell types were associated with acute exacerbations and disease course in pulmonary fibrosis.

We searched retrospectively non-elective hospital treatment periods of pulmonary fibrosis patients with acute deterioration of respiratory symptoms. Inclusion criteria were met in 237 patients, who had been treated in Oulu University Hospital or Oulaskangas Hospital between 2008 and 2017. 58% of patients had IPF and the rest some other type of pulmonary fibrosis, of which rheumatoid arthritis-associated pulmonary fibrosis (11%) or asbestosis (10%) were the most common subtypes. In addition, we examined mast cells that are known to be involved in the development of inflammatory and scar changes in the lungs from lung tissue specimens of 47 IPF patients.

Acute exacerbation of pulmonary fibrosis was the most common reason for hospital treatment period, and it was diagnosed in 128 pulmonary fibrosis patients. Other common causes for hospitalizations were acute worsening of respiratory symptoms without changes related to acute exacerbation and lower respiratory tract infections.

We also collected data on bronchoalveolar lavage (BAL) inflammatory cell counts of pulmonary fibrosis patients. BAL basophils were associated with increased risk for acute exacerbations and mortality. BAL lymphocytes examined during acute exacerbation were linked with a more favorable prognosis, whereas BAL neutrophils were associated with elevated risk for mortality. In addition, it was observed that the number of lung tissue mast cells was declined during acute exacerbation of IPF compared with the lung tissue specimens obtained in the stable phase of the disease.

The study provided significant new information on the number of pulmonary fibrosis patients in Northern Ostrobothnia, the distribution of fibrosis types, prognosis and acute exacerbations. New perspectives on the role of inflammatory cells in the course of the disease were revealed. In the future, our results can be utilized in the planning of the treatment of the pulmonary fibrosis patients. The information provided by this study may also be of particular importance now that the indications for pulmonary fibrosis drugs are expanding from IPF to other pulmonary fibroses.