Interstitial lung diseases (ILD) are diverse and have different causes, most of which are unclear. Interstitial lung disease and infection are like a pair of difficult brothers and sisters, often entwined and difficult to distinguish strictly. Some interstitial lung diseases are actually caused by infections; many patients with interstitial lung diseases are particularly susceptible to various pathogenic bacteria and are often aggravated by infections. These patients are often severely co-infected and difficult to treat. Therefore, infection in ILD patients is often an important factor limiting their outcome. In response to this problem, the author has reviewed the relevant literature, combined with personal clinical experience, to discuss some rough understanding.
I. The role of infection in the pathogenesis of interstitial lung disease: there are often two situations.
1, infection may be the cause of certain interstitial lung diseases.
Including viruses, bacteria, mycoplasma, chlamydia, etc., with viruses being the most common.
(1) Viruses: Patients with severe acute respiratory syndrome (SARS), clinically presenting as acute respiratory distress syndrome (ARDS), have pathological changes extremely similar to ARDS and acute interstitial pneumonia (AIP). The etiology is a novel coronavirus (SARS-CoV), which causes early exudative alveolar inflammation and later interstitial fibrosis. ooi et al. 2005 reported that human immunodeficiency virus (HIV) infection can first present as interstitial pneumonia and dry mouth, therefore routine screening for HIV antibodies is emphasized in the differential diagnosis of ILD. Unusual interstitial pneumonia (UIP) is the most common type of idiopathic interstitial pneumonias (IIPs), and although its etiology is unclear, risk factors are also associated with many viruses, including influenza virus, parainfluenza virus, cytomegalovirus, EBV, HIV, measles virus, herpes virus, and hepatitis virus. Interstitial lung disease in children, although uncommon, is mostly associated with viral infections, especially respiratory syncytial virus, parainfluenza virus and EBV.
(2) Bacteria: It has been reported in the literature that Legionella infection is one of the high-risk factors for idiopathic pulmonary fibrosis (IPF); our hospital has also found cases of interstitial pulmonary fibrosis remaining after Legionella pneumonia.
(3) Mycoplasma and Chlamydia: Although it is not certain that they can directly cause ILD, they are at least one of the risk factors.
2. Secondary infections are an important cause of acute exacerbations in patients with ILD and are often either
(1) Because many ILD patients have their own immune deficiencies, they are prone to various infections, which can trigger exacerbations. popa V et al. 2002 reported 148 cases of recurrent respiratory infections, 29 of which were in patients with ILD, accounting for 19.6% of all cases, much higher than the infection rate in the general population (0.8%; p < 0.05). Of these 29 ILD patients, 20 had IPF and all had IgG subtypes (IgGSCs) defects. Eight of them were treated with immunoglobulin intravenously, and clinical manifestations, physiological indices, imaging changes, and even histological lesions improved to some extent.
(2) During the process of hormone therapy, the immune function of the body was further suppressed, making it more vulnerable to pathogenic attack. In particular, they are prone to “cold and flu”, followed by fever, sometimes high fever, increased cough and sputum, and marked shortness of breath. In some patients, the lesions in the lungs expand rapidly and the disease worsens progressively until death. Faustova et al. isolated 175 strains of Haemophilus influenzae from the sputum of patients with various acute and chronic interstitial lung diseases and normal subjects, of which in acute interstitial lung disease, variant strains I, II and III could be isolated. In acute interstitial lung disease, variant strains I, II and III could be isolated, with variant II strains predominating ((56.4%); whereas in chronic ILD, various variant strains could be isolated, but variant II and III strains were predominant (58.7%); in normal subjects, untyped strains were predominant. This suggests that different bacterial variant types may have different pathogenicity.Tamara et al. reported in September 2005 at the 15th ERS meeting that 37 sputum specimens from 22 patients with IPF were quantitatively cultured and the sputum positivity rate reached 81.8% (27/37), of which one pathogen was found in 44.4% and two and more pathogens were found in 55.6% of the specimens . Among the pathogens, Streptococcus pneumoniae accounted for 29.6%; Haemophilus influenzae 14.8%; Staphylococcus 7.4%; aerobic-negative bacilli 48.1%; Nymphomonas sputum was found in 66.6% of cases, half of which reached the level of pathogenic count necessary for diagnosis (≥104 CFU/ml). It is believed that infection plays a very important role in the acute exacerbation of the disease in patients with ILD, and therefore It is emphasized that anti-infective therapy should be the basic treatment measure for patients with ILD. Among the more than 800 ILD patients treated in our department from 1998 to 2007, about 20% of the cases had acute exacerbations during treatment, and about 3% of them progressed rapidly and died without treatment, similar to those reported by Japanese scholars. Our department has summarized 60 patients with interstitial lung disease treated with hormone from March 2005 to August 2005, and sputum culture was routinely performed. 21 patients were found to have positive sputum bacterial culture, and the bacterial detection rate was 35.0%; among them, 7 cases had both bacteria and fungi detected, and 2 cases had both bacteria detected; 11 febrile patients had blood culture, and 3 cases were positive (1 case of E. coli and 2 cases of S. epidermidis). Thirty cases had positive sputum fungal culture, with a detection rate of 50%. This shows that the rate of secondary infections during hormone therapy in these patients is very high and should be given sufficient attention.
The above evidence suggests that infection by multiple pathogens plays a crucial role in the occurrence, development and prognosis of interstitial lung disease. In recent years, scholars at home and abroad have gradually focused on the problem of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). In 2007, the International Idiopathic Pulmonary Fibrosis Clinical Research Network organization jointly published a view on issues related to AE-IPF, suggesting that the causes of acute exacerbation of IPF are not clear at present, and there are several possibilities for analysis There are several possibilities.
First, it may be a pathological process of the pre-existing disease itself.
Second, it may be an acute exacerbation induced by some clinically undiscovered causes, such as viral infections, especially herpes virus, and inhalation of gastric contents.
Third, certain factors that directly damage lung tissue, such as lung biopsy, can also induce acute exacerbations. Although there is a tendency to consider AE-IPF as an “acute exacerbation” that excludes infections and other causes, no direct clinical basis for the pathogenesis of AE-IPF has been found, and the presence of infections cannot be completely excluded. Therefore, the exact cause of AE-IPF and the mechanism of its occurrence need to be further investigated.
Diagnosis of ILD co-infection
The difficulty in diagnosis is that it is very difficult to distinguish whether the disease is caused by an acute exacerbation of ILD itself or by a pulmonary infection when the disease progresses rapidly. In most cases, the two coexist and are mutually causal. That is, there is both infection and progression of the pre-existing condition. The infection may induce the expansion of the pre-existing lesion; while the progressing lesion is treated with immunosuppressive drugs such as corticosteroids secondary to a more severe secondary infection, creating a vicious cycle. Usually the following points can be used to help determine this, but when both conditions are present in combination, their application is limited.
Individual cases without co-infection can also appear hyperthermia: the judgment is that a variety of antibiotic treatment is ineffective, and the addition of hormones lesions are quickly absorbed, and the body temperature rapidly decreases.
4. Reliability of sputum examination.
Is the bacteria or fungi found in the sputum the causative agent of the lower respiratory tract infection? There are several methods to help determine this.
(1) Also use lower airway sampling, such as fiberoptic bronchoscopy under the line of anti-pollution brush or anti-pollution lavage sampling for quantitative culture, if and sputum culture for the same pathogenic bacteria, basically can be identified as the real pathogenic bacteria.
(2) Percutaneous pulmonary puncture for pathogenic organisms.
(3) Blood culture should be performed at the same time, and the positive bacteria should be the pathogenic bacteria.
(4) Quantitative culture of qualified sputum specimens with colony count ≥104 CFU/ml can be considered as pathogenic bacteria.
(5) When the above methods cannot be implemented, a comprehensive judgment can be made by combining clinical manifestations, sputum properties and treatment effects.
(3) Treatment of co-infection
1.If it is clearly caused by infection: there are two cases.
(1) The etiology of infection is clear, and targeted anti-infective drugs are available.
(2) If the pathogen of infection is unknown, the infection must be controlled with broad-spectrum anti-infective drugs first, and then treated with targeted drugs after the infecting bacteria are clear.
(2) If both the infection and the progression of ILD itself are considered, and the infectious agent cannot be identified for a while, a two-pronged approach must be taken.
That is, corticosteroids are increased and broad-spectrum antibiotics are applied at the same time. If fungal infection is combined, antifungal drugs should be added.
IV. Prophylactic anti-infective treatment in the absence of infection in ILD.
There are two situations.
1. Prophylactic anti-infective drugs, including: cephalosporin antibiotics, quinolone antibiotics, isoniazid and sulfonamides, are applied at the same time as high-dose hormones during hospitalization. Prevent fungal infection with fluconazole or itraconazole if necessary.
2. During outpatient oral hormone administration, if the prednisone dose exceeds 30mg/d, cephalosporin or quinolone antibiotics should be used to prevent bacterial infection; if the dose exceeds 10mg/d, tuberculosis prophylaxis should be used, mainly for oral administration.
In summary, infection and ILD are closely related and often cause each other, resulting in a vicious circle, which is one of the important causes of death in ILD patients. Therefore, anti-infective therapy is one of the important measures in the treatment of ILD, mainly for the prevention of possible and control of infections that have already occurred.