Non-absorbing, slow-absorbing and recurrent pneumonia: infectious and non-infectious pathogens
S1 Non-resolving or slowly resolving pneumonia
Refers to the persistence of abnormal radiographic manifestations of the lung beyond the time expected for the lesion to be absorbed. It is a clinical syndrome in which, despite at least 10 days of antibiotic treatment, “focal infiltrative shadows that coincide with some of the clinical manifestations of acute lung infection (e.g., fever, cough, malaise, and/or dyspnea) do not resolve within the expected time frame”.
II. Host factors
The rate of CAP dissipation is largely determined by host factors (e.g., age, comorbidities, etc.) and is an independent predictor of mortality. The dissipation rate of peripheral x-ray lesions is approximately 50% in mycoplasma and 41% and 60% in pneumococcal pneumonia with or without bacteremia, respectively. Only 1/3 of patients with Legionella pneumonia have lesions that completely dissipate at 4 weeks. Delayed resorption of imaging lesions and deterioration at the onset are usually characteristic of Legionella pneumonia.
III. Dissolution rates of pneumonia with different pathogens
1. Streptococcus pneumoniae
Streptococcus pneumoniae is the main causative agent of CAP, accounting for 30-70% of pneumonia and is the most common cause of death in CAP. Host factors such as advanced age, extreme debility, immunosuppressive therapy, and the presence of severe comorbidities can worsen prognosis and delay dissipation of imaging lesions. Bacteremia or multilobar pneumonia can delay the dissipation of lesions and increase mortality. Age, alcoholism, and COPD are independent factors in delayed lesion dissipation. x-ray deterioration is common in patients with bacteremia.
2. Legionella
Of all the pathogens causing CAP, Legionella pneumonia has the slowest dissipation, and progression and deterioration of the lung lesions on X-ray is one of the radiographic features of Legionella pneumonia. Despite appropriate treatment, progression can occur in 29-100% of patients. At the beginning, mainly lamellar alveolar infiltrates are seen, and the lesions continue to progress and may outgrow realistic signs or spread to adjacent lobes and may involve the contralateral side. The lesions may last up to 30 days before they are resolved, with the peak of most chest abnormalities occurring 2-7 days after onset. Although the prolonged and worsening course of the disease may reflect a delay in effective treatment, the radiographic presentation of the lesion may also be progressive when clinical treatment is prompt and effective.
Typically, only 1/3 of patients with Legionella pneumonia have complete resolution of the chest x-ray lesion at 4 weeks, and almost half of patients have abnormal chest changes lasting longer than 12 weeks. Their rate of absorption is highly variable. A few are delayed up to 6 months. In immunocompromised patients, outbreaks of Legionella pneumonia, prolonged disease course and necrotizing pneumonia with cavitation are more likely to occur.
3. Mycoplasma pneumoniae
Mycoplasma pneumoniae accounts for 1/3 of CAP. Mycoplasma pneumoniae affects adolescents and young adults differently, with faster uptake of mild pneumonia lesions (with or without specific antibiotics). In several early studies evaluating the uptake of chest x-ray lesions in Mycoplasma pneumoniae pneumonia, 8-17% of patients had worsening chest x-ray lesions even with effective antibiotics at the start, and delayed lesion progression with effective antibiotic therapy was more common, up to 40%. Although the time to lesion resolution varies, 63-98% of patients have complete lesion resolution by 8 weeks. In 2 studies, chest X-rays returned to normal at 12 and 20 weeks in all patients.
Radiographic abnormalities are associated with the clinical course of the disease. In one study, the absorption of mediastinal lymph node enlargement or dense shadows around the hilum was found to be slow, and the rate of complete absorption of interstitial infiltrative changes on chest X-ray at 4 weeks was 58%, compared with 26% for alveolar infiltrates. In a retrospective analysis of 100 serologically positive patients with mycoplasma pneumonia, patients were classified according to their clinical presentation, and those with typical symptoms of pneumonia (fever, cough and X-ray showing solid pulmonary changes) had a good outcome with antibiotic therapy, with complete absorption of the lesions in 5-14 days.
Most patients with mycoplasma CAP have rapid resorption of chest X-ray lesions, especially in acute pneumonia. Atypical patients may present with a prolonged course and persistent abnormal chest X-rays. Sickle cell disease, absence of spleen, or severe immune system deficiencies are at risk for sudden outbreaks or ineffective antibiotic therapy.
4. Chlamydia pneumoniae
The incidence of chlamydial CAP has been reported to be 2-8%. Because mycoplasma serologic testing and culture cannot be routinely performed, there is less awareness of Chlamydia pneumoniae infection. Chest X-ray signs of Chlamydia pneumoniae pneumonia often show a small number of lamellar infiltrates in subsections of the lung, and severe multilobar involvement is rare. A diagnosis of Chlamydia pneumoniae CAP is less likely in those with chest X-rays longer than 6 weeks.
Chlamydia psittaci pneumonia (parrot fever) is an acute infectious disease caused by Chlamydia psittaci and is clinically rare, but pneumonia with a history of exposure to birds and non-resorbable pulmonary lesions should be considered as a possibility by giving the disease.
Diagnosis is resistant to a history of exposure or relevant occupational history, and the recently developed serological test has some diagnostic value. Mycoplasma psittaci pneumonia has a faster rate of chest x-ray absorption than Streptococcus pneumoniae pneumonia, but slower than mycoplasma pneumonia.
5. Staphylococcus aureus and methicillin-resistant Staphylococcus aureus
Staphylococcus aureus CAP accounts for 2-10% of hospitalized CAP patients. Previously healthy adults rarely develop S. aureus CAP, but it can be seen in patients with complications from influenza or with specific risk factors (e.g., age >65 years, long-term nursing home residence, intravenous drug use, or those with comorbidities). Comorbidities can cause defects in the host’s local defenses (pulmonary disease or post-influenza) or systemic defenses (e.g., diabetes mellitus, chronic renal failure). X-rays of S. aureus pneumonia are not specific, but form necrotizing pneumonia, abscess chests, and cavities. Pulmonary effusion is the characteristic change of S. aureus pneumonia in children.
Both methicillin-susceptible and drug-resistant Staphylococcus aureus can cause CAP. patients on long-term antibiotics, extremely debilitated and long-term nursing home residents are susceptible to developing MRSA infections. The most common risk factor for developing MRSA infection while hospitalized is having lived in a health care home within the previous 12 months.
IV. Non-infectious slow-absorbing or non-absorbing pneumonia
1, lung tumor
2. Occlusive fine bronchitis with mechanized pneumonia
Occlusive bronchiolitis with mechanized pneumonia (BOOP) typically presents with persistent dry cough, dyspnea, and other symptoms (such as fever, malaise, and weight loss) for more than 2 weeks-6 months and may show focal alveolar infiltrates on chest x-ray, similar to CAP. BOOP can be a complication of CAP or can originate from inflammatory conditions (such as Legionella pneumophila infection, mycoplasma infection, or viral infection), the exposure to certain drugs or autoimmune diseases. Thus, BOOP may be the host’s way of generating an inflammatory response to airway injury.
Chest x-ray presentation is variable and nonspecific. 60-80% of patients present with alveolar-like infiltrative shadows in one segment, multiple segments, or lobes, sometimes confused with CAP because the alveolar infiltrate may be wandering, self-generating or shrinking, or seemingly effective on antibiotic therapy. 20-30% of cases present with diffuse reticular nodular-like shadows, 4-10% of cases present with a diffuse reticular nodular 20-30% of cases present with diffuse reticulonodular shadows, 4-10% of patients have normal chest radiographs or only hyperinflation signs. Dense alveolar infiltrates are more common in patients in the acute phase and are treated well with corticosteroids, whereas diffuse reticulonodular or interstitial changes are seen in chronic BOOP and are treated less effectively.
3. Allergic pneumonia (exogenous allergic alveolitis, HP)
is an immune-mediated lung disease caused by repeated inhalation of organic antigens or occupational and environmental pathogens. Acute HP is characterized by clinical features such as fever, cough, elevated peripheral white blood cell count, or infiltrative lung shadows within 4-12 hours of antigen exposure. The symptoms reappear after this exposure to the antigen. The typical presentation on chest X-ray is bilateral alveolar or interstitial infiltrative-like changes. Symptoms and imaging changes in the acute phase are easily confused with CAP.
Among the many HP, the most typical is farmer’s lung. Farmers inhale 75,000 mycobacterial spores per minute in a moldy, dry environment, most of which are thermophilic radiolarians, and this organism is the most common and important cause of farmer’s lung morbidity, with a prevalence of 8%. Similarly, pigeon feeder’s lung can occur after exposure to pigeon antigens, with an incidence of 6-15%.
Unlike acute HP, chronic HP resembles interstitial lung fibrosis, unlike CAP. which is caused by repeated and continuous exposure to antigens. It develops gradually over months or years with cough, dyspnea, chest radiographs showing interstitial infiltrates in both lower lungs, restrictive ventilatory dysfunction and hypoxemia. X-rays of the subacute or chronic phase changes are dominated by linear or small nodular shadows and cystic changes. Emphysema, pulmonary heart disease or fatal respiratory insufficiency may occur.
In acute HP, the BAL cell count is increased and the majority of the increase is in lymphocytes, up to 40% or more, and among the lymphocytes are mainly CD8+ cells.
Possible criteria for diagnosis: 1) history of exposure to environmental or occupational allergens; 2) precipitating antibodies on serological examination; 3) increased lymphocytes in BAL; 4) disappearance of symptoms after removal from the allergen.
4. Pharmacogenic pneumonia
Many drugs and banned substances can cause infiltrative changes in the lungs, which may or may not have clinical symptoms and can be easily confused with CAP. Several drugs that can cause acute HP have been clinically, BAL, and histologically confirmed (e.g., methotrexate, furantoin, gold agents, azosulfapyridine salicylate, etc.). The recovery of the disease is facilitated by the elimination of the precipitating factors. Severe or progressive cases may be treated with corticosteroids.
The drugs fludarubine, leucovorin, bleomycin and amiodarone are known to cause toxic pneumonia. Respiratory symptoms caused by chemotherapy drugs are difficult to confuse with CAP. Chronic amiodarone pneumonia is easily distinguished from infectious pneumonia, but the limited alveolar infiltrates, fever, and severe dyspnea of acute amiodarone pneumonia are easily confused with CAP.
5, chronic eosinophilic pneumonia
6.Acute eosinophilic pneumonia
7.Pulmonary vasculitis
Systemic necrotizing vasculitis syndrome (SNV)
The imaging changes of SNV are highly variable, often clinically febrile, and easily confused with CAP. A few SNVs, particularly Wegenar’s granulomatosis (WG), allergic granulomatous vasculitis (Churg-Strauss syndrome,
CSS) and microscopic polyangitis (MPA), which predispose to pulmonary involvement.
Pulmonary vasculitis is often associated with circulating anti-neutrophil cytoplasmic autoantibodies, which are called antineutrophil cytoplasmic antibodies (ANCA). the affinity of ANCA for different antigens helps in the identification of different types of SNV. Indirect immunofluorescence produces two fluorescent forms: cytoplasmic ANCA (c-ANCA) and perinuclear ANCA (p-ANCA). c-ANCA, whose target antigen is mainly specific for proteinase-3 (PR3), is highly specific for granulomatous vasculitis (especially WG) and is also positive in a few patients with MPA or CSS. p-ANCA, whose primary antigen is myeloid, is a specific proteinase 3 (PR3). The main antigen of ANCA is myeloperoxidase, which is not specific and is seen in many non-vascular inflammatory diseases, collagenous vasculitis and inflammatory bowel disease.
(1)
Wegener’s granulomatosis
Approximately 70-85% of WG patients may have pulmonary involvement, with a minority of patients having only infiltrative pulmonary shadows without symptoms. The typical presentation has upper respiratory symptoms, and X-rays often show single or multiple nodular shadows (visible cavities), sometimes with systemic symptoms and pulmonary infiltrative changes, in which case it is easily misdiagnosed as CAP. other presentations include pleural effusion, block shadowing, tracheal or bronchial stenosis, pulmonary atelectasis he alveolar hemorrhage (referred to as pulmonary capillitis).
The typical WG presentation is a triad of renal, upper and lower respiratory tracts, and limited WG may present with involvement of only 1-2 sites. The upper respiratory tract may present with symptoms of chronic rhinitis, otitis media or rhinorrhea, a benign process, but can cause hearing loss, saddle nose deformity or tracheal stenosis. Patients with renal damage can present with proteinuria and microscopic hematuria; significant renal insufficiency occurs rarely (<20%), and glomerulonephritis can occur in more than 2/3 of patients, 30% of whom require dialysis treatment. Common multi-organ involvement includes non-necrotizing arthritis (60%), skin damage (40-50%), eye damage (20-50%), central and peripheral nervous system symptoms (10-34%), cardiac involvement (10-15%), or gastrointestinal symptoms (5%). 1/3 of patients have fever, malaise, or weight loss.
c-ANCA-PR3 is highly specific (90%) and sensitive (60-92%) for WG, and its titer correlates with disease activity, but not exclusively. ESR and CRP, although not specific, can be used for the assessment and follow-up of disease activity.
Pathologic histologic changes in WG small vessel vasculitis include: small arteritis, small phlebitis, and capillaritis; granulomatous inflammation; and extensive necrosis. It can lead to narrowing or obstruction of the vascular lumen. Although WG predisposes to invasion of the upper respiratory tract, the rate of positive upper respiratory tract biopsies for diagnosis is <20%, and the rate of positive transtracheal biopsies is even lower (<10%). Open lung biopsy is feasible in patients with limited lesions and has a diagnostic positivity rate of >90%. Renal tissue biopsy is mainly for glomerulonephritis, with small renal artery granuloma or vasculitis changes seen in 10% less frequently.
(2)
Churg-Strauss syndrome (allergic granulomatous vasculitis)
The classic triad of CSS: severe asthma; small and medium-sized arterial and venous inflammation and necrotizing granulomas in the lungs and extrapulmonary organs; increased eosinophils in peripheral blood or tissue. 30-70% of patients present with limited alveolar infiltrates, which can be confused with CAP. Extrapulmonary organ involvement, increased vascular eosinophilia and increased ESR should raise suspicion of CSS.
All patients have allergies or asthma, and 70% have a history of sinusitis or allergic rhinitis that occurs months to years before the onset of systemic disease. As vasculitis worsens, so does asthma, and 90% of patients may have pulmonary involvement, mainly in the form of cough, fever, weight loss, and fatigue. There may also be cutaneous involvement (65%), peripheral or central nervous (40-50%), cardiac (30-50%), renal 50% and abdominal organs (20-40%). Blood eosinophils and ESR are elevated in the acute and remission phases, and most patients are positive for circulating ANCA (c-ANCA and p-ANCA).
The pathological histology of CSS is characterized by necrotizing vasculitis and granulomas of small vessels, and extravascular tissue may have eosinophils and fenestrated histiocytes. The disease is distinguished from other vasculitides by the presence of abundant eosinophil infiltration and granulomas. Treatment with cyclophosphamide and corticosteroids is commonly used.
(3)
Microscopic polyangiitis
MPA (formerly known as microscopic polyangiitis or polyangiitis overlap syndrome) presents with glomerulonephritis >90%, pulmonary capillaritis 30-50% and circulating c-ANCA or p-ANCA. other manifestations include leukocytotic vasculitis, oral ulcers and peripheral neuropathy. These features are rare in typical nodular polyarteritis.
MPA involves small vessels or microvessels (capillaries, small arteries, and small veins), and large vessel involvement is uncommon. Although the clinical and histological changes are similar to those of WG and CSS, there is no granuloma.
(4)
Alveolar hemorrhage syndrome
Alveolar hemorrhage syndrome (diffuse alveolar hemorrhage,
DAH) can be caused by different immunologic and non-immunologic diseases. In DAH syndrome, 40-55% are complicated by SNV, especially WG and MAP. in immune DAG syndrome, 18-32% are Goodpasture syndrome, a known anti-glomerular basement membrane antibody disease. The differential diagnosis is shown in Table 2. clinical presentation is characterized by rapid onset, progressive dyspnea and hypoxic respiratory failure. hemoptysis and iron deficiency anemia are common, but not universal features. Chest radiographs show focal or diffuse alveolar infiltrates, often suggesting diffuse capillaritis and alveolar hemorrhage. Autoimmune DAH is often associated with acute progressive glomerulonephritis (rapidly
DAH is not a common cause of alveolar infiltrates, but can be life-threatening and timely diagnosis and treatment is essential.
The differential diagnosis of DHA is extensive and therefore requires a thorough workup. Firstly, fiberoptic bronchoscopy is required in order to determine the site and extent of bleeding, and bronchoscopy can reach the site of the lesion to exclude infectious factors. This is followed by serological tests, including antinuclear antibodies, ANCA and anti-glomerular basement membrane antibodies, as well as urinalysis and renal function. If anti-GBM antibodies or ANCA are not performed, biopsy of the organ is required. , , and
The presence of renal insufficiency, microscopic hematuria with urine sediment or erythrocyte tubularity may be indicative of RPGN, and early percutaneous renal biopsy should be performed. Its histopathology is nonspecific, but immunofluorescence staining is helpful in identifying pulmonary-renal hemorrhagic syndrome. Patients who are critically ill or who cannot undergo percutaneous renal biopsy may be treated empirically with methylprednisone shock (pending serologic report) or other relevant site biopsy.
For the diagnosis of DAH, it is controversial whether to perform a lung biopsy using surgical methods such as open chest or thoracoscopy. Lung biopsy specimens may show alveolar hemorrhage and capillaritis, and these manifestations lack specificity to distinguish the many causes of capillaritis (e.g., SNV, SLE, anti-GBM disease, idiopathic or immune complex-mediated RPGN). The presence of granulomas, necrosis, or eosinophilia again aids in the diagnosis of WG or CSS. Surgical lung biopsy is contraindicated in critically ill patients with severe DAH and may be replaced by fiberoptic bronchoscopic BAL. appropriate clinical presentation combined with granulomatous visible blood, blood stains or bloody BAL lavage fluid in the airways and iron-containing yellow cells is highly suggestive of the diagnosis of DAH. Life-threatening DAH is treated with high-dose methylprednisolone shock therapy. oral corticosteroids and cyclophosphamide are the only treatment options for SNV DAH. Anti-GBM disease is treated with a combination of cyclophosphamide, corticosteroids, and plasma exchange.
S2 Recurrent pneumonia
I. Definition and background
Recurrent pneumonia is defined as 2 or more pulmonary infections with an interval of at least 1 month between complete resolution of interstitial chest X-ray infiltrates or absence of symptoms. Some authors believe that the interval between recurrences should be 1 year and that there is a pathophysiological relationship between the occurrence of pneumonia. Recurrent pneumonia is clearly a re-infection of the lungs, with a brief period of recovery between infections in which the patient is quickly re-infected by the same pathogen.
Recurrent pneumonia is more common, with the incidence of recurrent pneumonia being 7.6% over 15 years of age and 14.5% under 15 years of age. In a classic study, 429 patients were hospitalized for 2 or more acute pneumonias in the last 11 years, of which 306 had 2 pneumonias and 123 had 3 or more pneumonias, with an interval of 4 weeks-12 years between recurrences, most of them occurring 2-4 years after the first pneumonia. The incidence of recurrent pneumonia is lower if the interval of onset is set at 1 year.
II. Etiology of recurrent pneumonia
1. Host factors
Rarely occurring in healthy individuals, COPD, bronchiectasis, chronic alcoholism, congestive heart failure and diabetes mellitus, HIV infection, malignant blood disorders, corticosteroid or immunosuppressive or cytotoxic drug therapy, splenectomy, multiple myeloma, chronic sarcoidosis, etc. are the causes of relapsing pneumonia.
2. Respiratory factors
Unilobar ones are often suggestive of isolated structural abnormalities, either intratracheal lesions or extratracheal compressions, with intratracheal foreign bodies being the most common in children. Intra-airway tumors, adenomas and malformations cause limited obstruction in the airways. Extrinsic pressure changes and middle lobe syndromes are common in bronchopulmonary carcinoma. Enlarged mediastinal and hilar lymph nodes secondary to tuberculosis or fungal infection may compress the middle bronchi and recurrent middle lobe pneumonia may occur. Other causes are COPD, alpha-antitrypsin deficiency emphysema, and bronchiectasis.
Other respiratory causes of recurrent pneumonia are bronchopulmonary isolation and bronchial cysts. Recurrent pneumonia in the posterior basal segment of the left lower lung is often suggestive of pulmonary isolation disease.
Immune or idiopathic pulmonary syndromes are often misdiagnosed as recurrent pneumonia, such as BOOP, alveolar protein sinker’s disease, allergic pneumonia, and CEP.
Allergic bronchopulmonary aspergillosis and radiation pneumonia are easily confused with relapsing pneumonia.
Acute radiation pneumonia often occurs 3-8 weeks after radiation therapy, with clinical manifestations of fever and infiltrative shadows, which usually, but not exclusively, occur at the site of radiation therapy exposure.
3.Non-pulmonary origin factors
Chronic alcoholism is the most common. There are also congestive heart failure, antiseptal defect, diabetes mellitus, chronic renal insufficiency, and thoracic deformity.
III. Diagnosis
The anatomic site of recurrent pneumonia is first determined; repeated pneumonia in the same location often suggests structural abnormalities of the respiratory system (e.g., endobronchial lesions, extratracheal pressure and obstructive lesions, bronchopulmonary isolation, or bronchial cysts). Chest CT and bronchoscopy help in the diagnosis of the former. Bronchopulmonary isolation usually requires an aortogram in order to determine the origin of the trophoblastic vessels, thoracic or abdominal aorta, to provide a basis for surgical treatment.
Recurrent pneumonia at multiple sites may be the result of misaspiration or province-wide disease. Patients considered for possible misaspiration should have an early barium swallow of the esophagus to understand the functional and anatomic integrity of the esophagus. Those with bronchiectasis should have a sweat gland test, serum immunoglobulin assay, or nasal mucosal biopsy. A history or finding of asthma indicates ABPA or CEP. and HIV, etc.