Pulmonary fungal disease I. Overview In recent years, invasive fungal infection (IFI) has continued to increase, which is closely related to the increase in the average life expectancy of human beings, the increase in the number of patients with immunodeficiency such as chemotherapy for oncology, AIDS and organ transplantation, and the widespread use of interventional therapy, broad-spectrum antibiotics, adrenal corticosteroids and immunosuppressive drugs. Once IFI occurs, antifungal treatment should be administered as early as possible, which is the key to reduce the morbidity and mortality of IFI. However, the clinical diagnosis of IFI is not easy, and it is often misdiagnosed as a bacterial infection, or the diagnosis is made only on the basis of sputum culture isolation of fungi, resulting in omission or overdiagnosis. For antifungal treatment, irrational use of drugs is also more common. IFI is a fungal infection that penetrates the normally sterile superficial tissues of the body and invades the deeper tissues and organs of the body, and its occurrence depends on the interaction of external pathogenic factors and human immunity. The most common type of IFI is invasive pulmonary fungal infection (IPFI), which is a fungal infection of the bronchopulmonary region caused by fungi, i.e., fungal invasion of the tracheobronchial tubes and lungs. It causes inflammation of the airway mucosa and inflammatory granuloma of the lung, and in severe cases, necrotizing pneumonia and even hematogenous dissemination to other sites. However, it is important to note that IPFI does not include pulmonary changes caused by fungal parasitism and allergy. Fungal parasitism refers to clinically immunocompetent individuals with chronic lung disease who have positive sputum fungal cultures, mostly for fungal parasitism in the respiratory tract, or called colonization; the latter refers to fungus as an allergen causing bronchial asthma attacks, such as allergic bronchopulmonary aspergillosis. Therefore, it has been suggested to use invasive fungal diseases (IFD) to replace IFI, which is a broader concept covering IFI and parasitic states such as metaplasia and fungal spheres caused by fungi. Similarly, IPFI is accordingly suggested to be called IPFD, and the latter can be divided into 2 types, primary and secondary. The former refers to pulmonary fungal diseases with normal immune function and with or without clinical symptoms, while the latter refers to pulmonary fungal diseases with host factors and/or impaired immune function, which are more common in clinical practice. [Pathogens] Fungi (fungus) are a class of eukaryotic cellular microorganisms that have cell walls and typical nucleus structure and can reproduce sexually or asexually. Most fungi are multicellular, a few fungi are unicellular; cytoplasm with endoplasmic reticulum, mitochondria Golgi apparatus; nucleus with nuclear membrane and nucleolus, and DNA and histone conjugated line chromosomes. Unicellular fungi include yeast type and yeast-like fungi; the former reproduce in a budding manner and do not produce mycelium; yeast-like fungi have extended budding tubes that do not shed with the mother cell and form pseudomycorrhizae. Multi-cellular fungi morphology is slightly more complex, mainly composed of mycelium and spores; mycelium morphology is one of the important signs of fungal classification, according to the function of mycelium can be divided into nutritional mycelium, aerial mycelium, reproductive mycelium three; spores are produced by the reproductive mycelium of a propagule. Some fungi have a layer of mucus outside the cell wall, its chemical composition and function is very different from the cell wall, for example, the pod membrane of Cryptococcus neoformans can be seen under the electron microscope 3~4nm microscopic fibers, radiating out of the cell wall, containing mannitol, xylose, uronic acid and other acidic polysaccharide chemical composition, this pod membrane is closely related to the pathogenicity of Cryptococcus neoformans. Fungal components are different from bacteria, polysaccharides account for 80% to 90%, with a small amount of protein, lipids and inorganic salts. The cell wall consists of a microfibrous skeleton of titin (chitin) and a matrix in its gaps, and titin is a straight-chain multimer of N-acetyl-D-aminoglucose. Filamentous fungi have a high content of chitin, which facilitates the growth of mycelium. The matrix consists of a variety of polysaccharides, mostly in complexes with proteins; the mannan-protein complex is the most abundant. The inner layer of the cell wall containing ergosterol cell membrane is the site of action of amphotericin, arylamides and imidazole antifungal drugs. Fungal culture does not require high nutritional requirements, need high humidity and oxygen, commonly used Sabo medium, but the growth rate is slow, generally need 1 ~ 4 weeks to form colonies; colonies have three types: ① yeast type colonies: larger and thicker than bacterial colonies, the appearance of wet and dense, mostly milky white, a few are pink. Because most unicellular fungal colonies are yeast type colonies, so microscopic examination to see round or oval single cells. ② Yeast-like colonies: unicellular fungi reproduce by budding, Pseudomonas albicans and a few other strains have extended budding tubes and do not detach from the mother cell and form pseudomycorrhizae, pseudomycorrhizae can reach into the medium. ③ filamentous colonies: multicellular fungi are formed filamentous colonies, larger than bacteria and actinomycetes colonies and loose texture, fluffy, felt, cotton wool, because the mycelium grows deeply so the colonies are closely connected to the medium, not easy to be picked up. Microscopic examination to see mycelium, part of the mycelium has spore growth. Colony morphology, color, structure is the reference of fungal species identification. Fungal mycelium and spores are not strong resistance to heat, 60 ℃ ~ 70 ℃ heating for an hour can be killed, and to dry, sunlight, ultraviolet light and some disinfectants are resistant; but to 2.5% iodine and 10% formaldehyde is more sensitive. Understanding the structure of fungi can help to elucidate their pathogenic mechanisms and provide information or basis for clinical diagnosis, treatment and prevention of fungal diseases. There are about hundreds of species of fungi that can cause human diseases. 【clinical manifestations】 Pulmonary fungal infection is often secondary to serious primary disease, symptoms and signs are often not characteristic, can have the following clinical manifestations: (1) flu-like symptoms: manifested as fever, chills, headache, runny nose, arthralgia, myalgia, etc.; (2) insidious infection: no obvious symptoms and signs, can be self-healing; (3) pulmonary manifestations: ① pneumonia or bronchitis: the most common, and general bacterial pneumonia is difficult to (3) Pulmonary manifestations: (1) pneumonia or bronchitis: the most common and difficult to distinguish from general bacterial pneumonia. There can be fever, cough, white sticky sputum or yellow pus sputum and other symptoms, wet rales can be heard in the lungs, which can be accompanied by a small to medium amount of pleural fluid; ② tuberculosis-like manifestations: the clinical manifestations of histoplasmosis, dermatophytosis and nocardia sometimes resemble tuberculosis, and there can be dry cough, hemoptysis, chest pain and other respiratory symptoms and afternoon hypothermia, night sweats and other “symptoms of tuberculosis poisoning “(3) Lung abscess and abscess chest: often acute onset, may have chills, high fever (mostly chills fever), cough, mucopurulent sputum, sometimes the sputum odor is obvious, hemoptysis is mostly blood in the sputum. Actinomycosis and septic thorax due to nocardia are prone to form sinus tracts in the chest wall; ④ tumor-like manifestations: such as pulmonary cryptococcal tumor, histoplasmosis, coccidioidomycosis, etc., which resemble peripheral lung cancer. Dermatophytosis, Aspergillus infection, etc. can destroy the ribs and vertebrae, similar to the metastatic cancer of bone destruction; ⑤ pulmonary embolism and pulmonary infarction: such as angiophilic Trichoderma, easy to invade the blood vessels, pulmonary infection often leads to pulmonary embolism or even pulmonary infarction, similar to pulmonary thromboembolism; ⑥ other: can cause diffuse interstitial lung lesions, or similar to nodular disease manifestations. The imaging manifestations of IPFI can be broadly divided into the following types: ① pneumonia type, showing small or large lamellar shadows in the middle and lower lung fields, which can involve multiple lung segments or lobes, mostly seen in Candida albicans and Aspergillus infections. ②Mass type, showing inflammatory masses, isolated lesions, resembling tumors, mostly seen in Cryptococcus, Histoplasma, etc. ③ Aspergillus globules, mixed by Aspergillus filaments and fibrous mucus, parasitic in the lung cavity or cystic dilated bronchus, round or oval, translucent area of semilunar or crescent shape formed between Aspergillus globules and cystic cavity, as a typical imaging manifestation of chronic Aspergillus infection. ④ pleurisy type, referring to the lesion near the pleura or due to invasion of the pleura by hematogenous dissemination, with manifestations such as pleural effusion and (or) pleural thickening, mainly Candida albicans, followed by Candida tropicalis infection. ⑤ Corniform type, X-ray or CT shows corniform changes, mostly in the middle and lower lungs, varying in size, mostly seen in histoplasma, cryptococcal and Candida infections. From the above imaging presentation, it can be seen that the changes of IPFI are not specific. However, invasive pulmonary Aspergillus infection has its own characteristics, and its pathogenesis is based on the invasion of small pulmonary vessels by Aspergillus and the formation of hemorrhagic pulmonary infarction, which can show typical imaging changes. The mechanism is that when the pulmonary small vessel infarction after the local formation of pulmonary nodules or solid lesions, often located in the periphery of the lung near the pleura, the lung is a single or multiple foci, hemorrhage around the lesions, in the imaging manifestation of the halo sign; about 10-15 days later the pulmonary nodular lesions or pulmonary solid areas began to liquefy, necrosis, imaging cavity or crescent sign. The above manifestations are often seen in the acute phase of infection, and CT is a powerful weapon to detect pulmonary aspergillosis and can be one of the main diagnostic bases for the diagnosis of invasive pulmonary aspergillosis infection. Therefore, in high-risk patients who have shown clinical signs, CT examination of the chest should be performed as early as possible, and timely diagnosis is the key to successful patient care. In addition, imaging signs of hairy glass-like interstitial lung lesions in both lungs with hypoxemia should be highly alert for Pneumocystis carinii infection.