Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

Background: The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. Methods: This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. Results: The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Conclusion: Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.

Efficacy and safety of caspofungin for the treatment of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). METHODS: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. RESULTS: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. CONCLUSIONS: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Pulmonary cryptococcosis complicated with pulmonary aspergillosis: a series of studies and a literature review.

BACKGROUND/OBJECTIVE: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. METHODS: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. RESULT: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). CONCLUSION: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

The convoluted process of diagnosing pulmonary mycosis caused by Exophiala dermatitidis: a case report.

BACKGROUND: Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important. CASE PRESENTATION: A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia. CONCLUSIONS: Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.

Identification of a novel drug-resistant community-acquired Nocardia spp. in a patient with bronchiectasis.

A previously unknown Nocardia species was isolated from the lung tissue and bronchoalveolar lavage fluid (BALF) of a 58-year-old woman with bronchiectasis and recurrent pneumonia. This Nocardia (GZ2020T), which grew readily in Columbia blood agar and could induce pneumonia in a mouse model, represents a novel Nocardia species, and its closest known relatives are Nocardia anaemiae NBRC 100462T, Nocardia pseudovaccinii NBRC 100343T and Nocardia vinacea NBRC 16497T. However, unlike all previously known species, GZ2020T is the first genus of Nocardia spp. that is not susceptible to multiple drugs but does show susceptibility to linezolid and moxifloxacin, and thus, GZ2020T potentially represents a substantial health threat to patients with bronchiectasis and immunocompromised individuals. Although the original pathogen source and method of spreading remain uncertain, a mode of transmission from the environment to humans could exist. Vigilance with respect to its spread in the population and the transmission of antibiotic resistance genes in the environment should be maintained.

Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls.

BACKGROUND: Viral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial. METHODS: Consecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive. RESULTS: Viral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39 °C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04). CONCLUSION: Respiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP.

Fatal interstitial lung disease associated with icotinib.

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.

[A pathogenic and clinical study of 882 cases of adult influenza-like illness in Guangzhou].

OBJECTIVE: This study was undertaken to describe the viral etiology and clinical features in patients with influenza-like illness (ILI) in Guangzhou. METHODS: The nasopharyngeal and throat swabs were collected from 882 patients presenting with ILI between January and September, 2009. Viral pathogens were cultured and identified by immunofluorescence technique using the Shell-Vial method. The clinical data were statistically analyzed. RESULTS: (1) Viral etiology. Of the 882 samples, 385 (43.7%) were confirmed to have at least one of the 9 different respiratory viruses detected. Among these viral isolates, 67.3% (259/385) were seasonal influenza A virus, 27.8% (107/385) were influenza B virus, and 1.3% (5/385) were human parainfluenza virus (PHIV) 1, 2, or 3. In addition, 2 cases (0.5%) of each adenovirus, HSV-1, enterovirus and respiratory syncytial virus (RSV) were also found in the samples. Co-infections with more than one virus were revealed in 8 (2.1%) of 385 samples tested, among them 6 samples were mixture of influenza A and influenza B, 1 sample was positive for both influenza B virus and HPIV-3, and 1 was for both adenovirus and RSV. Seasonal influenza B virus appeared endemic between March and May, and seasonal influenza A virus became dominant between June and August. (2) Clinical features. The percentage of patients aged from 18-30 years was much higher than that of other age groups. The most common symptoms were moderate fever and sore throat, followed by cough. The percentage of upper respiratory infection and pneumonia was 88.4% (727/882) and 10.7% (95/882) respectively. Clinical features did not discriminate between patients with seasonal influenza A and those with influenza B virus infection. The average numbers of leukocytes and lymphocytes were lower in the group positive for influenza viruses than in virus negative group. The patients with adenovirus, HPIV and RSV infection were significantly younger. No rash was observed in patients with enterovirus or HSV infection. CONCLUSIONS: (1) Seasonal influenza virus was the major viral etiologic agent of ILI in Guangzhou during the first 9 months in 2009. Influenza B and A viruses seasonally prevailed in spring and summer, respectively, while other viral etiologic agents appeared to be sporadic. (2) The analysis of clinical features in patients with ILI indicated that fever was the most common symptom, with body temperature varying greatly, and may be associated with evident respiratory and occasionally systemic symptoms. Among the cases with viral infection, the upper respiratory presentation was universal, and pneumonia was frequently noticed.