Immunodeficiency pneumonia

　　1. In the diseases with recurrent respiratory tract infections, 1% to 2% are caused by primary immunodeficiency diseases, among which immunodeficiency refers to various diseases caused by damage to the immune defense mechanism due to congenital, hereditary, and other reasons.

　　2. Due to the increasing incidence of tumors, advances in treatment, improvements in the diagnosis and treatment of autoimmune and other immune-related diseases, breakthroughs and developments in organ transplantation, especially the prevalence of HIV/AIDS, the continuously increasing and accumulating immunocompromised hosts (ICH) have caused pneumonia, which has become a global huge challenge.

　　1. Upper respiratory tract infection

　　About 90% are caused by viruses, and bacterial infections often occur secondary to viral infections. The disease can occur in all seasons and at any age. It is transmitted through droplets containing viruses, mist, or through contaminated objects. It often occurs when the body's resistance is reduced, such as when chilled, tired, or rained on, and the virus or/and bacteria that are already present or侵入 from the outside grow and reproduce rapidly, leading to infection. The prognosis of the disease is good, with self-limitation, and usually recovers in 5-7 days. It often leads to secondary bronchitis, pneumonia, and paranasal sinusitis. A few people may have complications such as acute myocarditis, nephritis, and rheumatic fever.

　　2. Lower respiratory tract infection

　　The number of antibiotics available for clinical choice is increasing, and the number of drug-resistant strains is also increasing significantly. Due to the use of high doses of cephalosporins, hospital infections, especially Pseudomonas aeruginosa and enterococcal infections, are increasing. The progress of serological and molecular biological research has greatly improved people's understanding of mycoplasma, chlamydia, and legionella infections. Fluoroquinolones, macrolides, and others have attracted people's attention. Whether it is lower respiratory tract infection or upper respiratory tract infection, the vast majority are caused by viruses and are called viral respiratory infections.

　　Congenital X-linked agammaglobulinemia

　　In 1952, Bmton first reported this disease, which occurs in male children due to X chromosome abnormalities, rather than abnormalities in the structural genes of immunoglobulins, hence the name. The incidence is about 1 in 100,000. The immunological characteristics of this disease are that B lymphocytes differentiate and停滞 at the pre-B lymphocyte stage, mature lymphocytes and plasma cells cannot be seen; serum immunoglobulins of all types are at low levels, and antibodies cannot be produced even with antigen stimulation; T lymphocytes and cell-mediated immunity are completely normal. Children are usually not affected for the first 3 to 4 months after birth due to temporary protection from maternal antibodies. After that, they show increased sensitivity to pathogens, with the most common being infections of the upper and lower respiratory tracts. Infections of the gastrointestinal tract, bone and joint infections, sepsis, meningitis, and others are also seen. The symptoms of patients may not be as severe as those of children with corresponding infections, and are characterized by chronic, recurrent attacks. Pneumonia dissipates slowly, and half of the patients have concomitant bronchiectasis. Common pathogens include Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and other types of staphylococci and streptococci. Other pathogens include undetermined Haemophilus influenzae, Salmonella, Pseudomonas aeruginosa, mycoplasma, and so on. There are also reports of early Pneumocystis carinii infection and persistent viral and fungal infections in late stages, but in general, these pathogens are very rare in this disease. The standard treatment for this disease is the substitution and supplementation of gamma globulin, and the use of antibiotics to control infections. The prophylactic use of gamma globulin can reduce the incidence of bacterial infections, but it is rarely useful for mucosal surface infections. Therefore, it is recommended that prophylactic use of gamma globulin be carried out before structural damage to the target organ, but the dosage and the serum immunoglobulin concentration that should be maintained to prevent infection have not yet been determined.

　　Second, common variable immunodeficiency

　　The disease was first reported in 1954 and is a congenital, but non-hereditary immunoglobulin deficiency with a confusing name. Other names include acquired hypogammaglobulinemia, idiopathic delayed immunoglobulin deficiency, and primary hypogammaglobulinemia. The etiology of CVI is unclear and differs from X-linked agammaglobulinemia. The number of B lymphocytes in most patients is normal or increased, but they cannot develop into secretory plasma cells. In some cases, B lymphocytes cannot proliferate or synthesize immunoglobulins, while in other cases, although plasma cells are seen producing immunoglobulins, they cannot be secreted. In a few patients, substances that inhibit B lymphocytes are found in the serum. After removing the inhibitory substances in vitro, the function of B lymphocytes returns to normal. In some cases, an increase in suppressive T lymphocytes is also found, and the significance of this in the pathogenesis is unclear. Interestingly, H2-receptor blockers can reduce the activity of suppressive T lymphocytes, and in some patients, the level of IgG increases after taking such drugs. The serum IgG level in patients with this disease is usually below 3.0 mg/ml or half the lower limit of normal, and the levels of IgA and IgM are variable. Usually, one or two immunoglobulins are abnormally low, and occasionally both are normal. CVI is one of the diseases associated with increased sweat chloride. Most patients with cystic fibrosis have increased gamma globulin, but about 20% of patients show a decrease.

　　Therefore, those with increased sweat chloride and low gamma globulin should have their lymphocyte function measured. The clinical manifestations of the disease are similar to X-linked agammaglobulinemia, but most symptoms appear after the age of 30, with half of the patients presenting with recurrent respiratory infections as the main symptom. Nearly 90% of patients experience recurrent bacterial pneumonia during the clinical course, 70% have sinusitis, 35% have otitis media, and sepsis is rare. Respiratory infections are mostly caused by Gram-positive encapsulated bacteria, but the pathogenicity of non-capsulated Haemophilus influenzae and mycoplasmas is increasing. Non-respiratory infections include meningitis, abdominal abscesses, urinary tract infections, and are all rare. However, more than half of the patients have chronic diarrhea, which may be due to the overgrowth of Giardia lamblia or non-enteric bacteria. CVI often accompanies various non-infectious diseases, such as non-caseating granulomas in the lungs, spleen, liver, and skin, bone cancer, thymoma, lymphoma, and various thyroid diseases. Intravenous gamma globulin is recommended as substitute therapy, but further research is needed on what level of serum immunoglobulins should be achieved and its relationship with infection.

　　Three, Selective Immunoglobulin Deficiency

　　Selective deficiency of various immunoglobulins is quite common, and many of the deficiencies do not show any disease state, such as selective IgG4 deficiency in the normal population can reach 25%. According to examinations of healthy blood donors, it is found that about 1 in every 700 people has selective IgA deficiency. However, literature reports indicate that patients with deficiencies of various immunoglobulins, including IgA, IgG2, IgG3, IgG4, IgM, IgE, etc., can be single deficiencies, but most are combined deficiencies. Selective IgA deficiency is defined as serum IgA

　　Four, Complement Deficiency Syndrome

　　Primary complement deficiency is very rare, and the clinical syndrome of C1, C2, C3 deficiency is similar to systemic lupus erythematosus, or certain other connective tissue diseases, but the difference is that anti-DNA antibodies do not appear. There is no significant increase in the susceptibility to infection in patients. If pneumonia occurs, it is often secondary to sepsis. Deficiency of C1q is often associated with hypogammaglobulinemia, and the deficiency of C1 inhibitor is very common. The clinical manifestation is hereditary angioedema, and mucosal edema of the respiratory tract can be fatal. The deficiency of C3 is related to infection, and the deficiencies of C5 to 8 and complement pathway defects are involved. The classical activation pathway and the alternative activation pathway converge at C3, so C3 plays a key role in the host defense mechanism. Type I C3 deficiency is seen in the congenital bilateral absence of the testes syndrome, also known as Klinefelter syndrome, which is caused by the lack of C3 inactivating factor leading to the continuous activation and consumption of C3. Type II C3 deficiency is often associated with lipodystrophy, due to the presence of serum C3 convertase, which leads to degradation. Patients with C3 deficiency have an increased susceptibility to encapsulated bacteria, often suffering from recurrent purulent infections in the respiratory tract, middle ear, meninges, and skin. C5 to 8 has the function of lysing pathogens, and its deficiency will inevitably weaken the clearance of pathogenic microorganisms, but isolated C5 to 6 deficiency is very rare. Complement pathway defects have been recognized in recent years and are seen in sickle cell anemia. Patients not only lack heat-stable lectin for Streptococcus pneumoniae and cannot produce an antibody response, but also have a reduced ability to compensate using the complement pathway.

　　Five, Congenital Thymic Hypoplasia

　　This disease is caused by the abnormal development of the third and fourth pharyngeal pouches as the embryonic origin of the thymus and parathyroid glands, and the complete clinical syndrome includes thymic hypoplasia, absence of parathyroid tissue, congenital heart disease, and facial畸形, known as DiGeorge syndrome. Immunologically, patients have a lack of blood T lymphocytes, with lymphocyte absolute count at the lower limit of normal, and a lack of T lymphocytes in the deep cortex of lymph nodes. The function of T lymphocytes, such as the proliferative response to phytohemagglutinin (PHA), is suppressed. Serum immunoglobulins are usually within the normal range, and the antibody response to allergens is normal or decreased. Most children are suspected of the diagnosis within a few days after birth due to cardiac abnormalities and hypocalcemic convulsions. Laboratory examinations can further provide evidence. Generally, most patients die within a month, and survivors (most of whom are incomplete) often suffer from cytomegalovirus and Pneumocystis carinii pneumonia as well as Gram-negative bacillary sepsis.

　　Sixth, severe combined immunodeficiency disease

　　This is a group of heterogeneous diseases characterized by decreased lymphocytes, lack of lymphoid tissue, suppressed thymus function, and decreased immunoglobulins. Both T lymphocytes and B lymphocytes are abnormal, belonging to X-linked or autosomal recessive genetic defects. Immunological abnormalities include defects in pluripotent stem cells that cannot develop into T lymphocytes and B lymphocytes, decreased lymphocytes with a large variation in numbers, decreased gamma globulin, and occasionally normal lymphocyte counts and normal or increased serum gamma globulin, but with reduced responses to antigen stimulation. Although the disease types have not been subdivided, two subtypes with biochemical abnormalities have been found.

　　1. Deficiency of adenosine deaminase

　　The thymus tissue can be seen to have lymphoid tissue, but it stops maturing. Adenosine deaminase is found in various cells of mammals. Its deficiency generally only affects lymphoid cells, and the mechanism of action is unclear. It may be that the deficiency causes the accumulation of metabolites such as deoxyadenosine triphosphate, which can kill mature lymphocytes.

　　2. Deficiency of purine nucleoside phosphorylase

　　Patients with SCID have a decrease in the number of T lymphocytes, a reduction in the response to mitogens or antigens, while the number of B lymphocytes and immunoglobulins are normal, thus similar to AIDS. Another rare variant of the disease is the combined deficiency of lymphocytes and neutrophils, known as 'reticulohistiocytic abscess.' Most SCID patients develop the disease within 1 year of age, with symptoms such as candidal infections of the mouth and skin, pneumonia, and diarrhea. Most patients die of purulent pneumonia or organizing pneumonia, and often have infections with Pneumocystis carinii or herpesvirus.

　　1. Active exercise

　　Appropriate exercise can increase fat consumption, reduce cholesterol deposition in the body, improve insulin sensitivity, and is beneficial for preventing obesity, controlling weight, adjusting blood lipids, and lowering blood pressure. It is an active measure for preventing and treating cerebral infarction. Patients with cerebral infarction should choose according to their physical condition and should engage in appropriate and moderate physical exercise and activities to the extent that they do not feel tired. It is not advisable to do intense exercise, such as sprinting or mountaineering, and can engage in aerobic exercises such as jogging, walking, soft gymnastics, and Tai Chi.

　　2. Early diagnosis and early treatment

　　Try to find the pathogen and carry out etiological treatment.

　　3. Quit smoking and limit alcohol

　　Cigarettes contain more than three thousand kinds of harmful substances. Nicotine in the smoke can stimulate the autonomic nervous system, causing vasoconstriction, increased heart rate, and elevated blood pressure. It also increases blood cholesterol levels, thereby accelerating atherosclerosis.

　　4. Reasonable diet

　　Pay attention to drinking plenty of water; eat a variety of foods, with grains as the mainstay.

　　1. Active exercise
　　Appropriate exercise can increase fat consumption, reduce cholesterol deposition in the body, improve insulin sensitivity, and is beneficial for preventing obesity, controlling weight, adjusting blood lipids, and lowering blood pressure. It is an active measure for preventing and treating cerebral infarction. Patients with cerebral infarction should choose according to their physical condition and should engage in appropriate and moderate physical exercise and activities to the extent that they do not feel tired. It is not advisable to do intense exercise, such as sprinting or mountaineering, and can engage in aerobic exercises such as jogging, walking, soft gymnastics, and Tai Chi.
　　2. Early diagnosis and early treatment
　　Try to find the pathogen and carry out etiological treatment.
　　3. Quit smoking and limit alcohol
　　Cigarettes contain more than three thousand kinds of harmful substances. Nicotine in the smoke can stimulate the autonomic nervous system, causing vasoconstriction, increased heart rate, and elevated blood pressure. It also increases blood cholesterol levels, thereby accelerating atherosclerosis.
　　4. Reasonable diet
　　Pay attention to drinking plenty of water; eat a variety of foods, with grains as the mainstay.

　　The diagnosis of immunodeficiency pneumonia, in addition to clinical manifestations, the best method is to detect the pathogen of infection, collect detailed medical history and physical examination data, and choose immunological examination on this basis.

　　In addition to conventional treatment for immunodeficiency pneumonia, attention should also be paid to the following aspects in diet: preference for light and simple food, eating more vegetables and fruits, reasonable diet搭配, ensuring adequate nutrition. In addition, spicy and刺激性 food should be avoided.

　　First, treatment

　　1. Antimicrobial treatment should be differentiated according to different situations and adopt different treatment strategies

　　(1) Acute fatal infection: Some primary immunodeficiencies are prone to sudden, refractory infections that can be fatal. For example, Wiskot-Aldrich patients are prone to infections with Streptococcus pneumoniae, Haemophilus influenzae, and other encapsulated bacteria. Antibacterial treatment should be based on the most likely pathogen, selecting potent bactericidal agents that cover these pathogens for intravenous administration, while supplementing immunoglobulins. After obtaining an etiological diagnosis, targeted and more sensitive antibacterial treatment should be adopted. Chronic granulomatous disease often occurs with severe staphylococcal pneumonia or infections in other parts, and penicillin resistant to enzymes or combined with rifampicin should be selected.

　　(2) Acute non-severe infection: Antibody deficiency and dysfunction of phagocytes often lead to acute respiratory infections in patients, including sinusitis, otitis media, mastoiditis, bronchitis, and pneumonia. Although these infections are not immediately fatal, they recur frequently, not only affecting the quality of life of patients but also causing damage to the structure and function of the respiratory organs. Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and some bacteria of the Neisseria genus are common pathogens. The difficulty of antibiotic treatment lies in the fact that these patients repeatedly use antibiotics, and the resistance rate increases. Therefore, culture isolation of pathogenic bacteria and antibiotic sensitivity testing are very important for the correct selection of antibacterial treatment.

　　(3) Chronic infection and its complications: The aforementioned acute infections often recur and are prone to become chronic, leading to pulmonary fibrosis, bronchiectasis, lung function impairment, and threatening life. In addition to adequate antibacterial treatment during acute infections, patients should have chest X-rays and pulmonary function tests followed up annually. Some advocate for intermittent or long-term use of antibiotics for prevention, but there is no definitive conclusion. There is a report of a patient with Job's syndrome suffering from severe staphylococcal lung abscess who was treated with cloxacillin for more than 8 years, achieving good results, and recurrence occurred as soon as the medication was stopped. Generally speaking, although it should not be universally promoted, antibiotic prophylaxis may be beneficial in selected cases, on the premise that: ① the etiological diagnosis is clear, and mainly caused by one type of bacteria; ② there are no significant adverse reactions after taking antibiotics; ③ the drug is not easily resistant. The author advocates that even for prophylactic use of antibiotics, sufficient doses should be used, and does not agree with some authors'主张 of low-dose prophylactic antibiotics. Sulfamethoxazole/trimethoprim (SMZ-TMP) is used to prevent Pneumocystis carinii pneumonia, and sulfadiazine, rifampicin, and clindamycin are used as prophylactic drugs for patients with abnormal phagocytes, especially those with abnormal phagocyte function, with several successful reports.

　　2. Immunotherapy

　　(1) Human blood gamma globulin: Substitution therapy with human blood gamma globulin is necessary for antibody deficiency patients. The combination of antibiotics and intravenous immunoglobulin (IVIG) is recommended as the standard treatment. Preventive IVIG in patients with congenital X-linked agammaglobulinemia and hypogammaglobulinemia can significantly reduce the incidence of infections. The use of high immune globulin (CMV) IVIG in organ transplant patients can reduce CMV pneumonia. The dose of therapeutic IgG is 400mg/kg. As an alternative treatment or for prophylactic use, it can be calculated according to the serum IgG level, and it is estimated that 100mg/kg IVIG per month can increase the serum IgG concentration by 200mg/dl. Due to the improvement of the production technology of intravenous preparations, IVIG does not require typing, making the risk of infections such as hepatitis virus, TIV, and CMV extremely low. Currently, intravenous treatment is advocated, which can avoid many adverse reactions of intramuscular injection and can be used at home, thus saving costs.

　　(2) Plasma: Due to the lack of pure preparations of various corresponding components in patients with various selective immunoglobulin deficiencies and complement deficiencies, plasma can be used as an adjuvant treatment.

　　(3) Transfer factor and thymosin: the former is a non-immunogenic, low molecular weight extract from human leukocyte lysate.

　　(4) Bone marrow, fetal, thymus, and fetal liver transplantation: successfully used in severe combined immunodeficiency, Wiskott-Aldrich syndrome, etc. The long-term efficacy is yet to be observed.

　　(5) Others: Adenosine deaminase and nucleoside phosphorylase can be applied to patients with metabolic defects, and high-dose vitamin C can be used for patients with high IgE syndrome and abnormal leukocyte chemotaxis. Recently reported, gamma interferon has achieved good effects in patients with chronic granulomatosis and is under further testing. Gene therapy for hereditary or congenital immune deficiencies is the most promising treatment method, but due to the relatively small number of cases of such diseases overall, the current research progress is not significant.

　　II. Prognosis

　　Most patients have underlying diseases, and with severe infections, the prognosis is poor.