With the development and increasing popularity of functional endoscopic sinus surgery (FESS), most of the clinical treatments for chronic rhinosinusitis (CRS) have gained long-lasting and stable efficacy. However, it is undeniable that the efficacy of some CRS is still unsatisfactory even after comprehensive treatment including FESS. One of the important aspects is immunological factors, including immunological abnormalities caused by congenital hereditary factors. The basic functions of the immune system include immune defense, immune self-stabilization, and immune surveillance, any of which can lead to immune dysfunction, resulting in diseases called immunodeficiency diseases (IDD). There are two main types of IDD: (1) primary immunodeficiency diseases (PID), also known as congenital immunodeficiency diseases, are genetically related, and most of them are monogenic. Secondary immunodeficiency diseases (PID), also known as acquired immunodeficiency diseases, can occur at any age and are mostly caused by severe infections, especially those that directly invade the immune system, malignant tumors, the application of immunosuppressive drugs, radiation therapy and chemotherapy. Immunologists have long been aware of such problems because the onset of most inherited diseases in the general population basically follows Mendel’s law, and CRS, as a group, has a proportionate incidence of inherited diseases. For example, primary immunological diseases (PID) is a congenital hereditary disease with an incidence rate of 1/5000 live births, and covers more than 150 diseases and 120 genes. Therefore, the CRS population must also include PID patients. It is for this reason that the first edition of the European position paper on chronic rhinosinusitis and nasal polyps (Eumpean position paper on rhinosinusitis and nasal polyps) was organized by the Eumpean academy of allergy and clinical Immunoloy (EAACI). rhinosinusitis and nasal polyps 2005, EPOS 2005), and has been continuously updated since then, demonstrating the role of immunologic factors in the pathogenesis of CRS. At present, the problems encountered in CRS can be summarized as follows: ① The efficacy of drug treatment in some CRS cases is not satisfactory, often good or bad, especially in a considerable proportion of pediatric patients; ② The anatomical factors constituting some of the causes of the disease (e.g., sinus stenosis, septal deviation, etc.) have been corrected after FESS treatment of CRS, but the efficacy of the disease is not satisfactory; ③ Unexplained persistent or refractory rhinosinusitis is not a cause of CRS. (iii) Unexplained persistent or refractory sinusitis. So are there congenital or genetic factors involved in the pathogenesis of these CRS patient groups? This brings us to the topic of immunodeficiency. Primary immunodeficiency disorders (PID) are divided into eight major categories, including combined immunodeficiencies, major antibody deficiencies, other well-defined immunodeficiency syndromes, immune dysregulation disorders, congenital defects in phagocyte number and function, natural immunodeficiencies, autoinflammatory disorders, and complement defects. PID has the highest prevalence of antibody defects, and common immunodeficiency diseases include: congenital dysgammaglobulinemia (also known as Bruton’s disease) and common variable immunodeficiency disease, which are major antibody defects, mostly due to primary B-cell deficiencies; DiGeorge’s syndrome, which is classified as an “other defined immunodeficiency syndrome”; and “other defined immunodeficiency diseases”, which are caused by primary B-cell deficiencies. DiGeorge syndrome is categorized as “other well-defined immunodeficiency syndromes”, which is dominated by primary T-cell defects; and severe combined immunodeficiency diseases, which have both T- and B-cell immunodeficiencies, are combined immunodeficiencies. Due to the complexity of the etiology of immunodeficiency diseases, the lack of specificity of clinical manifestations, mainly with recurrent, severe infections as a prominent manifestation, so in order to timely detection of PID patients, many foreign countries have successively proposed PID clinical early warning symptoms, which are summarized in the following 10 aspects: (1) frequent CRS (≥2 times/year), and each episode is more serious; (2) frequent ear infections (≥8 times/ year); (3) frequent pneumonia (≥2 episodes/year); (4) localized infections that have not responded to antibiotic treatment for more than 2 months; (5) growth retardation in infants and young children; (6) recurrent cutaneous lesions or organ abscesses; (7) familial primary immune deficiencies; (8) oral ulcers, and children who are susceptible to thrush even after the age of 1 year; (9) lack of lymph nodes or tonsils; and (10) ataxia. In terms of the range of otolaryngologic disorders, frequent sinusitis, otitis media, and pneumonia are the main clues suggesting the presence of PID among the reported clinical warning signs of PID. Therefore, as a clinician, whenever the possibility of combined immunodeficiency in CRS is considered, a more detailed examination according to the classification of immunodeficiency diseases should be performed, and specific immunologic evaluation protocols should be investigated together in coordination with the relevant departments if necessary. Routine immunologic evaluation includes a complete blood count and classification, measurement of serum immunoglobulin (including IgG, IgA, and IgM) levels, and flow cytometry analysis (including CD 3+, CD 4+, and CD 8+, CD 19+CD 16+/CD56+). Diagnosis can be made in the majority of patients using routine immunologic evaluations, and if the diagnosis cannot be made and an association with immunologic factors is still considered, further measurements of specific antibody levels and delayed-type hypersensitivity skin tests can be performed. The clinical complications of CRS with PID are most often antibody deficiencies, making serum immunoglobulin level testing particularly important. For the detection of specific antibody defects and its clinical application [5-7], more studies have been conducted abroad, while in China, it has not really taken off. Some authors conducted anti-pneumococcal antibody titer tests on 129 patients diagnosed with chronic sinusitis with poor drug treatment and surgery, and found that 36 cases were at or above the normal baseline level, while 93 cases (72%) were below the baseline level. Of these 93 cases, 24 were lost to follow-up, and the other 69 cases underwent pneumococcal vaccination and had their antibody titers tested again by blood sampling 6 weeks after the vaccination. The results indicated that 54 cases showed an immune response and 15 cases (11.6%) had no immune response, and it was initially deduced that these 15 cases were specific antibody defects. For example, for patients over 2 years of age who were suspected of having a specific antibody deficiency despite normal serum immunoglobulin values, a specific antibody deficiency could be considered if less than 7 out of 14 pneumococcal serotypes showed a response after a certain period of time after standard pneumococcal vaccination despite an antibody titer of ≥1.3 μ/mL. The management of such patients may include intravenous infusion of IG (immunoglobulin) if necessary. CVID, or common variable immunodeficiency disease, is basically considered in patients older than 2 years of age who have a significant decrease in total serum IgG (2 SDs below the standard age) and low IgA and/or IgM, and who have a poor or no response to immunization. The management of this type of disease is basically the same as above, i.e., prophylaxis and, if necessary, intravenous infusion of IG. In addition to the above 10 common clinical warning symptoms, different parts of the infection, different age groups can also suggest certain immune function defects, such as repeated episodes of otitis media and chronic sinusitis difficult to control with antibiotics, more suggest that there may be humoral or cellular immune deficiencies, especially in adult patients may be more gammaglobulinemia or common variable immunodeficiency disease. Secondly, different pathogenic microbial infections may also suggest certain immune deficiencies, e.g., Candida infections are often suggestive of T-cell or phagocyte deficiencies. Since the spectrum of immunodeficiency diseases is quite broad, even with the most advanced methods, it is not possible to ensure that “one misses a million”, as a clinician is the most important thing is to receive the CRS and poor outcome, must be based on the patient’s so-called early warning symptoms to revise the diagnosis and treatment ideas, to carry out the etiology of the investigation, which is very important part of the immunological examination. Immunologic examination is one of the most important elements. It is worth pointing out that some rare genetic diseases in the field of rhinology, which are very difficult to deal with and the effect of surgical treatment is very limited, should also be emphasized. Primary ciliary dyskinesia (PCD): the most common is Kartagener’s syndrome, which consists of a triad of visceral transposition, bronchiectasis and sinusitis. These patients are characterized by persistent rhinosinusitis with watery rhinorrhea and otitis media. Cystic Fibrosis (CF): Almost 100% of patients with this disease have combined sinus disease, with nasal polyps being the most common. patients with CF often have impaired mucociliary clearance due to abnormal cellular chloride transport and secondary bacterial colonization, leading to sinusitis. ③ Young’s syndrome (Young’s syndrome): the main features – intermittent obstructive sperm deficiency, chronic sinus-bronchial disease, nasal polyps and bronchiectasis. The clinical features are: frequent chronic sinusitis in childhood; common recurrent lung infections with clinical manifestations of intractable cough and sputum; although most patients still have X-ray manifestations of bronchiectasis in adulthood, the clinical symptoms are significantly reduced; and lung function is only mildly impaired. Attention to immunologic factors in the pathogenesis of chronic sinusitis (including such diseases due to heredity) and the means of their evaluation will help clinicians to have one more idea and one more approach when dealing with cases in which drug therapy is ineffective or even surgery has been performed, but the efficacy of the treatment is still unsatisfactory, and to accumulate valuable material for the eventual adoption of comprehensive means of attacking recalcitrant chronic rhinosinusitis.