The case report describes an atypical pulmonary infection without the classic sulfur granules associated with pulmonary actinomycosis. The patient received four months of guideline-concordant penicillin therapy, yet the lesion showed no measurable reduction on imaging. Following multidisciplinary discussion and positron emission tomography-computed tomography to characterize the disease and identify other suspicious lesions, he underwent video-assisted thoracoscopic surgery with right upper lobectomy. Intraoperative pus culture and repeated high-abundance metagenomic sequencing confirmed S. odontolytica.

After surgery, the patient received an additional 24 weeks of oral amoxicillin-clavulanate. At six-month follow-up, the report states that he remained clinically and radiologically free of recurrence. The investigators concluded that combining special histochemical staining with metagenomic sequencing may assist diagnostic evaluation in sulfur granule-negative pulmonary actinomycosis that resembles lung cancer. They also reported that a low number of sequencing reads in bronchoalveolar lavage fluid did not exclude invasive infection complicated by an encapsulated abscess in this case.

These findings come from a single case and therefore do not establish the reliability of the diagnostic approach, define optimal timing for surgery, or demonstrate that resection plus prolonged antimicrobial treatment benefits similar patients generally. The case involved one patient with diabetes and a persistent pulmonary lesion initially considered highly suspicious for malignancy. Based on the available abstract, the proposed role of timely surgical resection and prolonged postoperative antimicrobial therapy remains limited to the selected case presented rather than validated as a broader treatment strategy.

Subject of Research: A single case of sulfur granule-negative pulmonary Schaalia odontolytica infection mimicking lung cancer.

Article Title: Sulfur granule‑negative pulmonary Schaalia odontolytica infection that mimics lung cancer with lack of radiological response to β‑lactam therapy: a case report

Article References: Li, G., Ye, B., Zhou, X., & Chen, G. (2026). Sulfur granule‑negative pulmonary Schaalia odontolytica infection that mimics lung cancer with lack of radiological response to β‑lactam therapy: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14494-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14494-x

Keywords: Schaalia odontolytica, pulmonary actinomycosis, case report, lung cancer mimic, metagenomic sequencing, bronchoalveolar lavage, penicillin therapy, surgical resection, amoxicillin-clavulanate, diabetes mellitus, Sulfur, granule

The research team, led by pulmonologist Homer L. Twigg III, took advantage of a unique resource: a CLIA-approved clinical bronchoalveolar lavage laboratory that serves clinicians across central Indiana. Bronchoalveolar lavage, or BAL, involves threading a bronchoscope into the airways and instilling saline to wash out cells and soluble proteins from the alveolar spaces, the site where gas exchange occurs. Since October 2020, the laboratory had been receiving BAL fluid from patients undergoing bronchoscopy as part of their clinical work-up for persistent pulmonary symptoms after COVID-19. The only requirement for inclusion in the study cohort was a documented positive SARS-CoV-2 PCR test at some point before the lavage was performed.

By May 2022, the investigators had collected 37 BAL samples from 37 different patients. Five of these were obtained less than 28 days after a positive test and were classified as acute infections, while the remaining 32 were collected between 28 and 730 days after diagnosis, with a median of 178 days. The samples were processed by cytocentrifugation to generate cell differentials, and specimens contaminated with more than 15 percent buccal mucosal or airway epithelial cells were excluded. Two control groups were used for comparison: five healthy volunteers undergoing research bronchoscopy, and seven patients whose clinical BAL samples predated the pandemic entirely.

The cellular analysis revealed that suspected post-COVID-19 lung disease splits into three distinct inflammatory phenotypes. The first was essentially a normal BAL cell differential, with no increase in lymphocytes and minimal neutrophil accumulation. The second was a neutrophilic predominant pattern, defined by neutrophils making up at least 10 percent of the total nucleated cell population and exceeding the lymphocyte fraction. The third was a lymphocytic predominant pattern, in which lymphocytes accounted for at least 15 percent of cells and outnumbered neutrophils. Among the 12 patients with elevated lymphocytes, 8 had markedly inverted CD4-to-CD8 ratios, a finding classically associated with hypersensitivity pneumonitis, nonspecific interstitial pneumonia, chronic viral infections, and cryptogenic organizing pneumonia. The two patients with elevated rather than inverted ratios had underlying conditions, sarcoidosis in one case and mycobacterial antigen-associated hypersensitivity pneumonitis in the other, both known to drive CD4-predominant alveolitis.

Perhaps the most striking result came from the search for viral remnants. Using a commercial ELISA with a sensitivity of 0.256 picograms per milliliter, the team measured SARS-CoV-2 spike protein in acellular BAL fluid. Spike protein was readily detected in unconcentrated lavage fluid from the post-COVID patients compared with controls, and the difference remained significant even after correcting for dilution by expressing concentrations as picograms per milliliter of epithelial lining fluid, calculated using the urea method developed by Rennard and colleagues. Remarkably, spike protein was detected up to 627 days after the initial diagnostic test, supporting the hypothesis that residual viral proteins persist in the lung long after acute infection has cleared. The authors note that expanded data on persistent spike and nucleocapsid proteins, as well as viral nucleic acids, in this same cohort are described in a separate submitted manuscript.

To probe the pulmonary antibody response, the investigators turned to the PepSeq platform, a highly multiplexed serological technique that uses libraries of thousands of DNA-barcoded peptides with next-generation sequencing readout. For these experiments, a human virome-wide assay comprising 15,000 peptides was employed, with samples sequenced to a depth of more than 50 reads per peptide and replicate samples showing a median Z-score concordance of 0.94. Of the first 23 post-COVID subjects tested, 14, or 61 percent, had anti-SARS-CoV-2 antibodies in their BAL fluid, including many with polyclonal responses targeting epitopes on both spike and nucleocapsid proteins. Because the unstructured 30-mer peptides used in PepSeq cannot generally detect antibodies against conformational epitopes, the team also measured neutralizing activity with the cPass assay, which tests the ability of a sample to block binding between spike protein and the ACE2 receptor. Eleven of the 37 BAL samples, or 30 percent, exceeded the assay’s 30 percent inhibition cutoff, while no control sample exceeded 18 percent, and there was complete concordance between neutralizing antibody detection and PepSeq positivity.

The clinical correlations, however, proved more elusive. All subjects underwent chest CT scanning before bronchoscopy, and the scans were reviewed blindly by a NIOSH B Reader radiologist and grouped into predominantly ground glass opacities, predominantly fibrotic or interstitial changes, an equal mixture of both, or other patterns. No clear association emerged between radiographic appearance and the type of inflammatory milieu found in the lung. Long-term outcomes, tracked through chart review as of January 1, 2026, included vital status, need for lung transplant, and need for supplemental oxygen. The BAL inflammatory pattern was unable to predict long-term outcome in this underpowered analysis, although an intriguing signal appeared: no early adverse outcomes were observed among subjects with a normal BAL differential. In unadjusted logistic regression, the odds of a good outcome relative to the neutrophilic pattern were 2.13 for the normal group and 2.24 for the lymphocytic group, with confidence intervals that crossed one.

The findings carry significant implications for how post-COVID-19 lung disease is studied and treated. Because the NASEM definition of long COVID adopted by the NIH RECOVER initiative is purely clinical, relying on symptoms and radiographic findings after documented infection, patients grouped together under that umbrella may in fact harbor fundamentally different processes. The authors suggest that patients with a CD8-predominant lymphocytic pattern may have cryptogenic organizing pneumonia and could respond to corticosteroids, while those with neutrophilic inflammation may have the usual interstitial pneumonia pattern described in surgical lung biopsies of post-COVID patients. Patients with normal lavage fluid, who underwent bronchoscopy because of persistent CT abnormalities, likely have stable scar tissue from their acute infection, which could explain why some post-COVID fibrotic changes fail to progress and may even resolve, echoing the experience after SARS-CoV-1.

The persistence of spike protein also fits into a broader picture of chronic viral antigen stimulation. Prior work has documented residual viral proteins long after other infections, including HIV Nef protein in the lungs of aviremic patients and residual antigen presentation following influenza. Autopsy studies performed a median of 39 days after infection found persistent viral genomic RNA in nearly all patients, and a systematic review detected SARS-CoV-2 RNA in various tissues in 5 to 59 percent of subjects up to six months after acute infection. Persistent antigen can sustain chronic inflammation through multiple mechanisms, including ongoing B and T cell responses, T cell exhaustion and immunosenescence, direct stimulation of macrophages through TLR2, and activation of the complement system, which could plausibly drive the neutrophilic inflammation seen in a third of the patients. Notably, some form of immunosuppression was prevalent in the cohort, affecting 28 of 37 subjects, which the authors suggest may contribute to failure to clear the virus.

The investigators are careful to acknowledge the limitations of their work. The cohort is small and underpowered for linking inflammatory patterns to outcomes, the samples were collected relatively early in the pandemic before widespread vaccination and when more virulent strains circulated, and the cPass 30 percent cutoff was developed for plasma rather than BAL fluid, making the neutralization findings exploratory. There is also no comparison cohort of previously infected patients without chronic lung disease. Still, the study demonstrates that post-COVID-19 lung disease exists in several immunologically distinct forms, that viral proteins can linger in the lung for up to two years, and that clinical presentation alone may be an unreliable guide to the biology underneath. Whether residual SARS-CoV-2 components drive these phenotypes, and whether SARS-CoV-2-specific immune responses can ameliorate the disease, is currently under study.

Subject of Research: Inflammatory and immunologic profiling of bronchoalveolar lavage fluid in patients with post-COVID-19 lung disease

Article Title: Inflammatory and immunologic analysis of bronchoalveolar lavage from patients with post-COVID-19 lung disease

Article References: Twigg, H. L., III, Wilson, R., Yu, A. Q., Li, W., Altin, J. A., Tarver, R. D., Knight, I., Smith, P. A., Fraser, M. E., Castelluccio, P., & Rie, J. (2026). Inflammatory and immunologic analysis of bronchoalveolar lavage from patients with post-COVID-19 lung disease. Frontiers in Microbiology, 17, Article 1923299. https://doi.org/10.3389/fmicb.2026.1923299

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1923299

Keywords: long COVID, post-COVID-19 lung disease, bronchoalveolar lavage, SARS-CoV-2, spike protein, viral persistence, neutralizing antibodies, PepSeq, pulmonary inflammation, interstitial lung disease, alveolar macrophages, immunosenescence

The genus Aspergillus is vast—453 species are currently recognized—and its spores are everywhere, floating in both indoor and outdoor air. Most people inhale them daily without consequence. But for the immunocompromised—transplant recipients, chemotherapy patients, those on biologic immunosuppressants, or individuals recently infected with SARS-CoV-2 or influenza—these airborne conidia can trigger anything from allergic bronchopulmonary aspergillosis to invasive pulmonary aspergillosis, a condition with staggeringly high mortality. Among the culprits, Aspergillus fumigatus dominates, causing roughly 70 to 80 percent of invasive cases and earning recognition from the World Health Organization as a critical-priority fungal pathogen. A. flavus, notorious for its aflatoxin production and predilection for warm climates, accounts for another 15 to 20 percent, while A. niger, though less frequently invasive, is gaining clinical relevance.

Diagnosing aspergillosis has long been an imperfect science. Clinicians rely on serological biomarkers such as 1,3-β-D-glucan and galactomannan, alongside culture, but these approaches suffer from nonspecificity or outright failure to detect the etiological agent. PCR-based methods—qPCR, multiplex PCR, nested PCR, droplet digital PCR, even next-generation sequencing—have emerged as powerful alternatives, yet each carries its own baggage: high cost, technical complexity, difficulty distinguishing colonization from true infection, and limited accessibility in developing countries where the burden of fungal disease is often greatest.

Enter SCAR markers—Sequence Characterized Amplified Region markers—a technology that converts the messy, reproducible-but-hard-to-interpret bands of RAPD-PCR (Random Amplified Polymorphic DNA) into clean, species-specific primer pairs. The approach is elegant in its simplicity: researchers run RAPD-PCR with arbitrary primers, identify a band unique to the target organism, clone and sequence it, then design primers that amplify only that sequence. The result is a diagnostic assay that is fast, cheap, and easy to interpret—qualities sorely needed in settings where sophisticated molecular infrastructure is scarce.

Castro-Fuentes and colleagues at the Universidad Nacional Autónoma de México, working with the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, applied this strategy to three Aspergillus targets: the section Fumigati (which includes A. fumigatus and its cryptic sister species), A. flavus, and A. niger. Using 80 Aspergillus isolates from their Molecular Mycology Laboratory collection—spanning Mexico, Argentina, France, Peru, and Cuba—plus reference strains from the American Type Culture Collection, they screened RAPD-PCR patterns generated with three arbitrary primers: OPF-01, P54, and 1253. Of 34 polymorphic patterns, only these three primers yielded bands that were consistently present across all isolates of their respective targets and absent from everything else.

The team excised the specific bands from agarose gels, purified them, cloned them into plasmid vectors, and sequenced them. BLAST analysis against GenBank confirmed their specificity: the 1000-base-pair fragment from OPF-01 recognized only section Fumigati sequences with 100 percent coverage and similarity; the 400-base-pair P54 fragment matched only A. flavus at 97.94 percent similarity; and the 1000-base-pair 1253 fragment aligned exclusively with A. niger at 98.18 percent similarity. From these sequences, the researchers designed primer pairs using the Primer3 program, adhering to strict design criteria—18 to 25 nucleotides in length, 40 to 60 percent GC content, and melting temperatures between 55 and 65 degrees Celsius—to prevent primer dimers, secondary structures, and nonspecific hybridization.

Three SCAR markers emerged: AfOPF-01₁₈₀, which amplifies a 180-base-pair band specific to section Fumigati; AfP54_193.1, which produces a 193-base-pair band recognizing A. flavus; and An1253₂₂₀, which yields a 220-base-pair band in A. niger and, notably, its close relative A. luchuensis. Specificity testing against a panel that included other Aspergillus sections—Flavi, Nigri, and species such as A. tamarii, A. tubingensis, A. lentulus, and A. hiratsukae—as well as unrelated medically important genera like Candida, Histoplasma, Coccidioides, and Sporothrix, confirmed that the markers did not cross-react. Sensitivity assays using serial dilutions of genomic DNA revealed a limit of detection of 0.005 nanograms per microliter for all three markers—impressively low for an endpoint PCR approach.

The real test came with clinical samples. The team analyzed 51 galactomannan-positive bronchoalveolar lavage (BAL) samples from patients evaluated for aspergillosis at the Mexican respiratory institute. Because fungal DNA concentrations in BAL fluid are often vanishingly small, the researchers performed a re-amplification step after the initial PCR. The AfOPF-01₁₈₀ marker detected section Fumigati DNA in 19 of 51 samples—37.25 percent positivity. AfP54_193.1 identified A. flavus in 3 of 51 samples, or 5.88 percent. An1253₂₂₀, despite its analytical specificity, produced no positive results in the clinical cohort—a silence the authors attribute to possible low fungal load, PCR inhibitors in the sample matrix, non-homogeneous distribution of the microorganism, or sample degradation during storage.

The implications are considerable. Section-level identification matters because cryptic species within section Fumigati—A. lentulus, A. udagawae, A. felis, A. hiratsukae, A. viridinutans—are morphologically indistinguishable from A. fumigatus yet differ in antifungal susceptibility, sometimes dramatically. The galactomannan test, the current clinical workhorse, identifies only the genus level, offering no species resolution. The AfOPF-01₁₈₀ marker, by contrast, provides section-level specificity that could guide empiric therapy while species-level markers like AfP54_193.1 refine treatment decisions further. The markers were also designed from autochthonous isolates, a point of epidemiological relevance given the high genetic variability observed across Aspergillus species, particularly A. fumigatus.

Still, the authors are careful to frame this as a preliminary feasibility study, not a validated diagnostic. The cohort was small and homogeneous, drawn exclusively from galactomannan-positive samples; there was no internal amplification control for the BAL specimens; the limit of detection was determined subjectively by band presence or absence; and the study lacked data on aspergillosis classification in the patients whose samples were used. Concordance with culture-based identification could not be assessed because diagnosis rested solely on galactomannan detection. Cross-reactivity with Aspergillus sections not represented in the specificity panel remains a theoretical concern. The researchers call for prospective, multicenter validation across diverse populations and sample types before the markers can be considered clinically deployable. Yet the core message is clear: SCAR technology, long used in plant pathology, herbal drug authentication, and food microbiology, may finally have a foothold in the diagnosis of one of humanity’s most underappreciated fungal threats—a tool that is low-cost, rapid, and interpretable with nothing more than a thermocycler and an agarose gel.

Subject of Research: Preliminary clinical evaluation of SCAR-type molecular markers for the identification of the section Fumigati, A. flavus, and A. niger in bronchoalveolar lavage samples

Article Title: Preliminary clinical evaluation of SCAR-type molecular markers for the identification of the section Fumigati, A. flavus, and A. niger in bronchoalveolar lavage samples

Article References: Castro-Fuentes, C. A., Duarte-Escalante, E., Frías-De-León, M. G., González-Villaseñor, M. D. C. A., Cabello-Gutiérrez, C., Palma, G., Meraz-Ríos, B., & Reyes Montes, M. D. R. (2026). Preliminary clinical evaluation of SCAR-type molecular markers for the identification of the section Fumigati, A. flavus, and A. niger in bronchoalveolar lavage samples. Frontiers in Tropical Diseases, 7, Article 1892022. https://doi.org/10.3389/fitd.2026.1892022

Image Credits: AI Generated

DOI: 10.3389/fitd.2026.1892022

Keywords: aspergillosis, Aspergillus, SCAR markers, molecular diagnostics, PCR, fungal disease, bronchoalveolar lavage, infectious disease, Preliminary, clinical, evaluation, SCAR-type

Chronic eosinophilic pneumonia, or CEP, occupies a distinctive niche in pulmonary medicine. The disease is characterized by dense infiltration of the lung parenchyma by eosinophils, the white blood cells best known for fighting parasites and driving allergic reactions. It typically strikes middle-aged adults, shows a marked female predominance, and is strongly linked to asthma and atopic disease, with up to two-thirds of patients carrying a history of asthma before the lung disease declares itself. Clinically, CEP follows a subacute to chronic course, unfolding over weeks to months with cough, progressive shortness of breath on exertion, and constitutional symptoms such as weight loss and fatigue. The classic radiological picture is equally recognizable: bilateral consolidations and ground-glass opacities clustered at the periphery of the lungs, hugging the pleural surface in a pattern that experienced radiologists can spot from across the reading room.

The diagnostic architecture of CEP rests on a tripod of findings. Because no universally accepted diagnostic criteria exist, clinicians generally require a compatible subacute clinical course, characteristic peripheral-predominant pulmonary infiltrates on imaging, and evidence of eosinophilic inflammation, either in the blood or in bronchoalveolar lavage fluid, while systematically excluding secondary causes of pulmonary eosinophilia such as drugs, parasites, and systemic autoimmune disease. In typical cases, the lavage findings are dramatic. BAL eosinophilia is usually marked, often reaching 40 percent or more of the recovered cells, and peripheral blood eosinophil counts commonly exceed 1,000 cells per microliter. When the clinical picture, the imaging, and the cellular evidence all align, lung biopsy is generally considered unnecessary, reserved for the minority of cases in which features are atypical or inconclusive. That reserve clause, as this case demonstrates, is where diagnostic danger lives.

The patient at the center of the report was a 61-year-old ex-smoker who arrived with two months of progressively worsening breathlessness on exertion and two weeks of a productive cough that would not relent, accompanied by weight loss. His medical history included asthma, managed with inhaled fluticasone furoate and vilanterol, along with type 2 diabetes treated with empagliflozin and metformin and hyperlipidaemia controlled with simvastatin for more than a decade. He reported no recent travel abroad and no consumption of raw or undercooked food, closing off the most common routes to parasitic lung infection. On examination, doctors heard bilateral fine inspiratory crackles but no wheezing, and they found none of the peripheral stigmata, purpura, mechanic’s hands, Gottron papules, Raynaud phenomenon, synovitis, or neurological deficits, that would suggest a connective tissue disease or vasculitis masquerading as lung disease.

Laboratory testing initially seemed to confirm the suspicion of CEP. The patient’s peripheral blood showed eosinophilia of 15 percent, corresponding to 1,314 cells per microliter, comfortably above the threshold commonly associated with eosinophilic lung disease. Chest radiography revealed bilateral peripheral patchy opacities with an upper-lobe predominance, and high-resolution computed tomography went further, demonstrating multifocal peripheral consolidations and ground-glass opacities with a subpleural predilection, along with traction bronchiectasis indicating that the process had been smoldering long enough to begin remodeling the lung’s architecture. Taken together, the subacute course, the blood eosinophilia, and the textbook peripheral distribution of disease made CEP the leading diagnosis on admission, and a reasonable one by any standard.

Then the bronchoscope told a different story. Bronchoalveolar lavage of the patient’s lung returned a cellular differential that was 85 percent neutrophils and only 6 percent eosinophils, a profile that belongs to bacterial pneumonia, not to eosinophilic lung disease. Autoimmune serology, including antinuclear antibody, proteinase 3-antineutrophil cytoplasmic antibody, and myeloperoxidase-antineutrophil cytoplasmic antibody, came back negative, and the total IgE level of 289 kU/L offered no signal of an allergic driver. Urinalysis showed neither haematuria nor proteinuria, and renal function was normal, further arguing against a systemic vasculitis. Confronted with neutrophil-predominant lavage fluid, the clinical team reasonably pivoted to an infectious explanation and initiated empirical treatment with amoxicillin and clavulanate. The antibiotics failed. Symptoms persisted, radiographic abnormalities did not budge, follow-up lavage microbiological cultures were negative, cytological examination identified no parasitic organisms, and stool examination for parasites was also unrevealing.

With the non-invasive pathway exhausted, the team turned to video-assisted thoracoscopic surgery, resecting a wedge of the left lower lobe for histopathological examination. What the pathologist found rewrote the case entirely. The tissue demonstrated an organizing pneumonia pattern, defined by intra-alveolar proliferation of fibroblastic foci, the plug-like clusters of immature connective tissue known as Masson bodies, accompanied by active immature fibrosis. Critically, woven through the interstitial and peribronchiolar regions was a prominent eosinophilic inflammatory infiltrate, with plasma cells and scattered lymphocytes in attendance. The alveolar architecture was relatively preserved, and, importantly, a blood vessel examined in the specimen showed an intact wall with no histological evidence of vasculitis, excluding one of the most dangerous mimics. Integrating the clinical course, the peripheral eosinophilia, the radiological findings, the histopathological features, and a thorough assessment for secondary causes, the physicians made the diagnosis of chronic eosinophilic pneumonia.

Treatment followed the established playbook for CEP. Intravenous methylprednisolone was commenced at 40 milligrams daily, a dose equivalent to prednisolone at 1 milligram per kilogram of body weight per day, then converted to oral methylprednisolone before discharge and gradually tapered over approximately two months. The response was swift and convincing. Symptoms improved progressively, and a chest radiograph obtained after roughly one month of corticosteroid therapy showed resolution of the bilateral peripheral opacities that had dominated the initial films. The trajectory underscores why making the correct diagnosis matters so much: corticosteroids, which are useless against bacterial pneumonia and potentially harmful, are precisely the right weapon against CEP, and delays in reaching the diagnosis translate directly into prolonged symptoms and unnecessary exposure to antibiotics.

The case’s most instructive twist lies in what the lavage fluid did and did not reveal. Although BAL eosinophilia is usually prominent in CEP, the authors note that considerable variability has been reported across published series, with eosinophil proportions ranging from as low as 12 percent to as high as 95 percent. There is a technical reason for this scatter: bronchoalveolar lavage samples only a limited portion of the distal airways and alveolar compartment, a tiny and possibly unrepresentative window onto a patchy disease process. A normal or atypical BAL differential, the authors emphasize, does not exclude microscopic abnormalities elsewhere in the lung tissue. The cellular profile of lavage fluid should therefore be interpreted in conjunction with the clinical and radiological findings rather than wielded in isolation, and when the lavage results clash with the broader picture, surgical lung biopsy may be justified in selected patients to establish the diagnosis definitively.

The report also untangles a second source of confusion, the relationship between CEP and cryptogenic organizing pneumonia. The two conditions share several clinical and radiological features, including subacute respiratory symptoms, pulmonary consolidation, and ground-glass opacities, which can complicate their distinction even for experienced clinicians. Histologically, however, organizing pneumonia is a non-specific pattern of lung injury that may occur in a variety of pulmonary disorders, CEP among them. Although eosinophilic infiltration of the alveolar spaces and interstitium is the characteristic histopathological hallmark of CEP, foci of organizing pneumonia with intra-alveolar fibroblastic plugs may also be present within it. The presence of an organizing pneumonia pattern on biopsy, in other words, does not automatically signify cryptogenic organizing pneumonia. In this patient, the combination of that pattern with prominent eosinophilic infiltration, alongside compatible clinical, radiological, and peripheral blood findings, anchored the diagnosis firmly in eosinophilic territory. For clinicians navigating the eosinophilic lung diseases, the message is blunt: lavage fluid is a supporting witness, not the judge, and when the evidence conflicts, the tissue still holds the final word.

Subject of Research: Diagnosis of chronic eosinophilic pneumonia with atypical bronchoalveolar lavage findings and an organizing pneumonia pattern on lung biopsy

Article Title: Chronic Eosinophilic Pneumonia: A Diagnostic Challenge With Atypical Bronchoalveolar Lavage Findings and an Organizing Pneumonia Pattern

Article References: Lin, Y.-T., Ou, W.-F., Liang, S.-Y., Hu, Y.-H., Chen, W.-C., & Chan, M.-C. (2026). Chronic Eosinophilic Pneumonia: A Diagnostic Challenge With Atypical Bronchoalveolar Lavage Findings and an Organizing Pneumonia Pattern. Respirology Case Reports, 14(10), Article e70780. https://doi.org/10.1002/rcr2.70780

Image Credits: AI Generated

DOI: 10.1002/rcr2.70780

Keywords: chronic eosinophilic pneumonia, bronchoalveolar lavage, organizing pneumonia, lung biopsy, eosinophilia, interstitial lung disease, corticosteroids, high-resolution computed tomography, cryptogenic organizing pneumonia, respiratory medicine, case report, differential diagnosis

Ulcerative colitis is well known for the symptoms it causes in the large intestine, but it belongs to a family of conditions whose influence is systemic. Extraintestinal manifestations affect up to 27 percent of patients, and among these, lung disease has been increasingly appreciated. One large cohort study of 563 patients with ulcerative colitis identified lung involvement in 5 percent, with organising pneumonia accounting for 1.8 percent. Yet that same study attributed nine of the ten organising pneumonia cases to drug-induced mechanisms, leaving open a fundamental question: can organising pneumonia arise as a primary, disease-intrinsic feature of ulcerative colitis itself, independent of any medication?

The new case suggests that it can. The 2025 update to the international multidisciplinary classification of the interstitial pneumonias, issued jointly by the European Respiratory Society and the American Thoracic Society, now explicitly lists ulcerative colitis among the secondary causes of cicatricial organising pneumonia, a histologically distinct entity. That formal recognition matters, because it provides a framework for attributing lung disease to the underlying bowel condition rather than defaulting to a drug reaction—a distinction with direct consequences for how patients are treated.

The patient at the centre of the report was a lifelong never-smoker with a ten-year history of ulcerative colitis pancolitis, maintained on a stable dose of mesalamine at 2.4 grams daily. She carried a concurrent diagnosis of rheumatoid arthritis, made five years after her colitis began, based on bilateral symmetric polyarthritis affecting fifteen small joints with finger nodules. Two biologic drugs, adalimumab and certolizumab, had been trialled and discontinued for lack of efficacy. Three months before admission, her pulmonary function tests had been entirely normal. Then she developed progressive shortness of breath over the course of a single month.

On admission, she required low-flow oxygen, and examination revealed crackles in both lungs. Crucially, a faecal calprotectin measurement obtained one month earlier stood at 62 micrograms per gram, below the 80 micrograms per gram threshold that identifies histological bowel activity—a biomarker-confirmed remission. Her systemic inflammatory markers, however, told a different story: C-reactive protein, erythrocyte sedimentation rate and white cell count were all elevated. High-resolution computed tomography of the chest showed bilateral interstitial haziness, predominantly in the mid and lower lung fields, representing clear progression from prior imaging that had shown only mild scattered scarring.

Diagnostic workup proceeded along two tracks. Bronchoalveolar lavage fluid revealed a differential cell count of 42 percent neutrophils and only 3 percent lymphocytes—a profile that would later prove important. A transbronchial cryobiopsy of the right lower lobe was performed, and the initial histopathological interpretation locally was fibrotic non-specific interstitial pneumonia, a diagnosis that prompted plans for antifibrotic therapy with mycophenolate and nintedanib. But when the slides were reviewed by expert pulmonary pathologists, the interpretation changed fundamentally. The expert consultation identified organising pneumonia, characterised by polypoid fibroblast plugs known as Masson bodies within the airspaces, with only mild background fibrosis and an absence of honeycomb change or fibroblast foci—the hallmarks that would have supported a diagnosis of usual interstitial pneumonia or fibrotic non-specific interstitial pneumonia.

That diagnostic reversal was directly consequential. The planned antifibrotic regimen was abandoned in favour of corticosteroid therapy, the standard treatment for organising pneumonia, which carries a five-year survival exceeding 90 percent when treated appropriately. The patient received three days of intravenous pulse methylprednisolone followed by oral prednisone with a planned six-month taper. Mesalamine was held as a precaution, but withholding the drug produced no clinical improvement on its own—further evidence against a drug-induced mechanism. Follow-up imaging at two months showed partial resolution of the bilateral infiltrates, with residual changes consistent with her pre-existing baseline scarring, and azathioprine was added as a steroid-sparing agent with the additional benefit of maintaining her colitis.

The authors lay out a careful argument for why this organising pneumonia was disease-intrinsic rather than drug-induced. First, mesalamine exposure had been stable for a decade; drug-induced pneumonitis typically appears within weeks to months of initiation or dose change. Second, discontinuation of the drug during hospitalisation brought no improvement, whereas corticosteroids were required for a response—inconsistent with the natural history of a drug reaction. Third, the 2025 classification now formally recognises ulcerative colitis as a secondary cause of cicatricial organising pneumonia. The case also extends the sole prior published report of organising pneumonia occurring after histologically confirmed ulcerative colitis remission, adding biomarker-confirmed remission, systematic drug exclusion, detailed lavage data and a complete autoimmune workup that reclassified the patient’s joint disease as ulcerative colitis-associated spondyloarthropathy rather than rheumatoid arthritis, removing rheumatoid-associated lung disease from the differential.

Perhaps the most scientifically intriguing observation is the lavage profile. Classic cryptogenic organising pneumonia typically shows lymphocytic predominance in bronchoalveolar lavage, with lymphocyte counts of 20 to 40 percent and only mild neutrophil elevation. This patient showed the reverse: 42 percent neutrophils and a mere 3 percent lymphocytes. Prior research has shown that secondary organising pneumonia carries lower lymphocyte counts than the cryptogenic form, and the authors hypothesise that ulcerative colitis-associated disease may carry a distinctly neutrophil-predominant signature reflecting immune cell trafficking along the gut-lung axis. Mouse studies lend plausibility to this idea: colitis has been shown to induce pulmonary neutrophil infiltration through interleukin-17 elevation and microbial translocation, and interleukin-6-driven, neutrophil-mediated pulmonary inflammation has been documented in murine models of colitis with bacteremia.

The case is also a cautionary tale about diagnostic uncertainty in interstitial lung disease. The discordance between the local reading of fibrotic non-specific interstitial pneumonia and the expert reading of organising pneumonia mirrors a documented pitfall of cryobiopsy interpretation: intraluminal Masson bodies within airspaces favour organising pneumonia, whereas interstitial fibroblast foci within the alveolar wall characterise the fibrotic pneumonias. The CAN-ICE trial found only fair between-center agreement for cryobiopsy-based diagnoses, with a kappa of 0.29. In this instance, expert pathology review changed the entire treatment trajectory, and the authors argue that such review should be considered routine whenever cryobiopsy-based diagnoses drive major therapeutic decisions. Two cases over thirteen years may reflect genuine rarity, the authors concede, but under-recognition is equally plausible, given that prior cohorts attributed drug causation without systematic exclusion criteria. For clinicians, the message is twofold: organising pneumonia can flare during biomarker-confirmed bowel remission, and drug-induced causes must be rigorously excluded before the lung disease is attributed to the bowel condition—because the correct diagnosis determines whether a patient receives antifibrotics or steroids, a fork in the road with very different prognoses.

Subject of Research: A case of disease-intrinsic organising pneumonia occurring during biomarker-confirmed ulcerative colitis remission

Article Title: Disease‐Intrinsic Organising Pneumonia During Biomarker‐Confirmed Ulcerative Colitis Remission

Article References: Jereisat, R. A., Ibrahim, N., & Dahdel, M. (2026). Disease‐Intrinsic Organising Pneumonia During Biomarker‐Confirmed Ulcerative Colitis Remission. Respirology Case Reports, 14(9), Article e70702. https://doi.org/10.1002/rcr2.70702

Image Credits: AI Generated

DOI: 10.1002/rcr2.70702

Keywords: ulcerative colitis, organising pneumonia, extraintestinal manifestations, gut-lung axis, cryobiopsy, interstitial lung disease, bronchoalveolar lavage, corticosteroids, ERS/ATS classification, mesalamine, inflammatory bowel disease, Masson bodies

Mesalazine, also known as 5-aminosalicylic acid or 5-ASA, has been a cornerstone of inflammatory bowel disease management for decades. It is prescribed to both quell active flares of ulcerative colitis and Crohn’s disease and to keep those diseases in remission over the long term. Because it is generally well tolerated, patients often take it for years with little thought. Yet the new report underscores that even this familiar molecule can provoke serious lung injury. Drug-induced eosinophilic pneumonia occurs when an offending medication triggers an influx of eosinophils into the alveolar air spaces and the interstitial tissue of the lungs, impairing oxygen exchange and producing cough, breathlessness, and infiltrates visible on chest imaging. Diagnosis typically rests on a compatible drug history, elevated eosinophils in peripheral blood or bronchoalveolar lavage fluid, characteristic imaging, and exclusion of infection and other causes.

What makes this case exceptional is timing. In the vast majority of reported instances, mesalazine-related lung injury emerges two to six months after treatment begins, a lag that can easily lull clinicians into overlooking the drug as a culprit. The literature contains only a handful of cases in which symptoms appeared within ten days of the first dose, and the present patient, whose cough began on day seven, now ranks among the earliest ever recorded. By the time she was referred to hospital on day 39, chest radiography showed worsening consolidation in the right upper lung field along with a pleural effusion. Computed tomography demonstrated diffuse consolidation concentrated in the right upper lobe. Her vital signs remained stable, with an oxygen saturation of 96 percent on room air, but her white cell differential told a striking story: eosinophils made up 37.8 percent of a total count of 9,700 cells per microliter, and her C-reactive protein was mildly elevated at 2.67 mg/dL.

To pin down the diagnosis, clinicians turned to bronchoscopy. Bronchoalveolar lavage returned fluid with a total cell count of 5.88 × 10⁶ per milliliter, of which an extraordinary 78.6 percent were eosinophils, a signature finding in eosinophilic lung disease. Transbronchial biopsy and transbronchial lung cryobiopsy, a technique that freezes a larger sample of lung tissue for histological analysis, revealed dense eosinophilic infiltration in both the alveolar spaces and the interstitium. Bacterial and mycobacterial cultures and cytology were all negative, ruling out infection and malignancy. With the drug withdrawn, the clinical course became its own confirmation: chest radiography began improving just two days after mesalazine was stopped, the patient’s cough resolved within a month, and pulmonary infiltrates and peripheral eosinophilia had normalized six weeks later, all without corticosteroid therapy. She was subsequently transitioned to vedolizumab, a gut-selective biologic, for her ulcerative colitis, and the pneumonia did not recur.

Behind this single patient stands a much larger body of evidence assembled by the reporting team. Searching MEDLINE and screening references from prior reviews, the authors identified 57 additional cases of mesalazine-induced lung injury, bringing the total analyzed to 58. The demographic picture is instructive: patients ranged from 14 to 84 years of age, with a median of 35 and a peak in the third decade of life, and women outnumbered men 34 to 24. Ulcerative colitis accounted for 84 percent of underlying diagnoses, with Crohn’s disease making up most of the remainder. Eosinophilic pneumonia was the most common pattern of injury, representing 43 percent of cases, followed by interstitial pneumonia at 27 percent and organizing pneumonia at 10 percent. Most patients, 67 percent, showed bilateral infiltrates, though unilateral disease, as in this case, does occur and can mislead clinicians toward an infectious diagnosis.

The timing data from that literature review are perhaps the most clinically valuable takeaway. While lung injury typically develops two to six weeks after initiation, roughly 10 percent of cases occur within the first two weeks, and only two cases on record, including this one, manifested within ten days. In a focused analysis of 18 well-documented eosinophilic pneumonia cases, symptom onset ranged from seven days to fourteen months, with 70 percent occurring within two months. The median cumulative dose at onset was 81 grams of mesalazine; the present patient had consumed only about 14 grams when her symptoms began. That discrepancy carries real mechanistic weight, because a reaction that ignores both the duration of exposure and the total dose ingested is the hallmark of hypersensitivity rather than toxicity.

That mechanistic distinction matters for how clinicians think about drug safety. Drug-induced lung injury generally arises through two principal pathways: direct cytotoxic damage to alveolar epithelial or endothelial cells, which tends to be dose-related, and immune-mediated inflammation, which can erupt unpredictably at any exposure level. The evidence points firmly toward the immune pathway for mesalazine. Researchers propose that the drug may skew immune signaling toward a Th2-dominant response, in which cytokines such as interleukin-5 drive the production, recruitment, and activation of eosinophils, ultimately seeding them in lung tissue. Pharmacokinetic data reinforce the plausibility of a hypersensitivity mechanism: approximately 20 to 30 percent of orally administered mesalazine and about 10 percent of rectal formulations are absorbed systemically, and eosinophilic pneumonia has been reported even after rectal administration, indicating that small systemic exposures can suffice to ignite the reaction.

The case also settles a long-standing question about the older drug sulfasalazine, a prodrug that is metabolized in the gut into mesalazine and sulfapyridine. When eosinophilic pneumonia occurred in patients taking sulfasalazine, toxicity was often attributed to the sulfapyridine moiety. But the accumulating reports of identical lung injury with mesalazine alone suggest that the 5-aminosalicylic acid molecule itself is capable of triggering the immune response. For the millions of patients with inflammatory bowel disease who take 5-ASA compounds worldwide, this reframing means that no formulation of the drug class can be considered free of pulmonary hypersensitivity risk, however rare that risk may be in absolute terms.

One intriguing wrinkle in the present case is the patient’s respiratory history. She had suspected bronchial asthma and used inhaled corticosteroids as needed, and her fractional exhaled nitric oxide, a noninvasive marker of eosinophilic airway inflammation, was elevated at 51 parts per billion. The authors caution that this reading may have reflected pre-existing asthmatic airway inflammation rather than pneumonia alone, and they note that only one previously reported mesalazine lung-injury patient had a history of bronchial asthma. Whether underlying allergic airway disease can accelerate the onset of drug-induced eosinophilic pneumonia remains uncertain, but the possibility offers a concrete hypothesis for future research and a reason for heightened vigilance in asthmatic patients starting the drug.

The practical message for clinicians and patients alike is one of awareness rather than alarm. Corticosteroids, the usual mainstay of eosinophilic pneumonia treatment, are not always necessary; simple drug withdrawal can be sufficient when respiratory status is stable, as this case demonstrates. Yet some patients have received prednisolone out of concern that stopping mesalazine might precipitate a relapse of their inflammatory bowel disease, illustrating the delicate balancing act physicians face. The authors’ conclusion is straightforward: eosinophilic pneumonia can develop early in the treatment course, and drug-induced lung injury should be considered whenever respiratory symptoms or pulmonary infiltrates appear during mesalazine therapy. For a drug taken daily by so many, recognizing that the lungs can protest within a single week of the first tablet may make the difference between a swift, uncomplicated recovery and a prolonged diagnostic odyssey.

Subject of Research: Rapid-onset mesalazine-induced eosinophilic pneumonia occurring seven days after drug initiation

Article Title: Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report

Article References: Inazaki, T., Takeda, K., Iwasaki, M., Tajima, H., Shionoya, Y., Hirama, R., Sato, S., Naito, A., Kawasaki, T., Ikari, J., Kageyama, S., Ikeda, J.-I., & Suzuki, T. (2026). Rapid Onset of Mesalazine‐Induced Eosinophilic Pneumonia Manifesting 7 Days After Initiation: A Case Report. Respirology Case Reports, 14(9), Article e70758. https://doi.org/10.1002/rcr2.70758

Image Credits: AI Generated

DOI: 10.1002/rcr2.70758

Keywords: mesalazine, eosinophilic pneumonia, ulcerative colitis, drug-induced lung injury, inflammatory bowel disease, bronchoalveolar lavage, hypersensitivity pneumonitis, 5-aminosalicylic acid, adverse drug reaction, respirology, eosinophils, case report

The culprit, when it was finally identified, turned out to be not one pathogen but two. Metagenomic next-generation sequencing, or mNGS, performed on fluid sampled from deep within his lungs detected Chlamydia psittaci, an intracellular bacterium better known as the cause of psittacosis or parrot fever. Meanwhile, conventional sputum culture grew extended-spectrum beta-lactamase-producing Escherichia coli, a multidrug-resistant Gram-negative bacterium whose enzymes can dismantle many of the penicillin- and cephalosporin-class antibiotics that form the backbone of pneumonia therapy. The combination is genuinely rare. C. psittaci pneumonia is uncommon even on its own, typically tied to contact with infected birds, and its coexistence with a drug-resistant enteric bacterium in the same diseased lungs created a therapeutic puzzle that standard treatment guidelines are not built to solve.

The patient’s avian exposure was the first clue that many clinicians might have missed. Long-term contact with pigeons is a recognized risk factor for C. psittaci, which birds carry asymptomatically in their gastrointestinal tracts and shed in droppings, feather dust, and respiratory secretions. Humans inhale the organism in dried aerosols, and the resulting pneumonia can range from a mild flu-like illness to fulminant respiratory failure. Because the bacterium lives inside host cells and grows slowly, standard cultures often fail to detect it, and serological tests require paired samples taken weeks apart, a luxury that a deteriorating patient in an intensive care setting cannot afford. In this case, the initial workup was entirely unrevealing, and the man was begun on empiric therapy with piperacillin-tazobactam, a broad-spectrum beta-lactam and beta-lactamase inhibitor combination, plus doxycycline, the tetracycline-class antibiotic that is the traditional mainstay of psittacosis treatment.

On paper, that regimen should have covered both organisms. Piperacillin-tazobactam retains activity against many ESBL-producing E. coli strains, and doxycycline targets C. psittaci directly. Yet the patient failed to improve, a clinical signal that something in the equation was wrong. It was at this point that the diagnostic team turned to metagenomic next-generation sequencing, a technique that sidesteps the need to culture an organism at all. Instead of trying to grow a specific microbe, mNGS extracts all genetic material from a clinical sample, in this case bronchoalveolar lavage fluid suctioned through a bronchoscope into the deepest airways, and sequences it in bulk. Bioinformatic pipelines then subtract human reads and match the remaining fragments against databases of microbial genomes, producing an unbiased census of everything living in the sample, bacteria, viruses, fungi, and atypical organisms alike.

The sequencing results were decisive. C. psittaci DNA was detected in the lavage fluid, confirming the intracellular pathogen that routine diagnostics had missed, while the parallel sputum culture independently confirmed the ESBL-producing E. coli. The dual findings forced a reassessment of the entire treatment strategy. Antimicrobial susceptibility testing of the cultured E. coli provided the second half of the evidence, showing which antibiotics the resistant strain would and would not respond to. Guided by this combined molecular and phenotypic picture, the clinicians adjusted therapy to a three-drug regimen of piperacillin-tazobactam, doxycycline, and levofloxacin, a fluoroquinolone that adds activity against both atypical organisms and resistant Gram-negative bacteria. Alongside the antimicrobial escalation, the team provided respiratory support and organ protection, the supportive scaffolding that keeps patients alive long enough for antibiotics to work.

The response was what every clinician hopes for but cannot count on in sepsis. The patient improved steadily and was ultimately discharged, a resolution that the authors attribute directly to the treatment adjustment guided by mNGS and susceptibility data. The case thus becomes a textbook argument for molecular diagnostics in severe pneumonia of unknown origin, particularly when a patient fails empiric therapy. Traditional culture-based methods remain indispensable for susceptibility testing, but they are blind to organisms that will not grow on artificial media, and they can take days to yield results that a critically ill patient may not have. mNGS compresses that timeline and broadens the net, catching zoonotic and atypical pathogens that no standard panel would think to test for.

Yet the report also carries a cautionary note about over-reading molecular results, one that reflects a growing tension in the era of ultra-sensitive diagnostics. The authors emphasize that detecting a multidrug-resistant organism in a respiratory sample should be interpreted cautiously, weighing the possibility of colonization against true infection. The human airway and gut harbor complex microbial communities, and E. coli can colonize the respiratory tract of hospitalized patients without causing disease. Distinguishing a bystander from a pathogen requires clinical correlation, meaning the organism’s presence must fit the patient’s illness pattern, inflammatory markers, imaging, and, crucially, the response to targeted therapy. In this case, the treatment failure on the initial regimen and the eventual improvement after adjustment served as the real-world test of whether the ESBL-producing E. coli was a genuine co-pathogen or an innocent passenger, and the clinical trajectory argued for its relevance.

The broader lesson extends beyond this single hospital room. Severe community-acquired pneumonia remains one of the most common reasons for intensive care admission worldwide, and a substantial fraction of cases never receive a confirmed etiological diagnosis, forcing clinicians into empiric choices that can miss atypical organisms or underestimate resistance. Patients with animal exposure, whether birds, livestock, or wildlife, represent a subgroup where the differential diagnosis widens considerably, encompassing zoonoses such as psittacosis, Q fever, and tularemia that routine testing rarely covers. The authors argue that in such patients who fail initial therapy, mixed infections including drug-resistant bacteria must be actively considered rather than assumed away, and that rapid etiological diagnosis through mNGS can meaningfully redirect care. The finding also underscores the quiet global march of ESBL-producing Enterobacterales, which have moved from hospital wards into community settings, meaning that resistance genes once confined to healthcare-associated infections can now appear in a farmer’s lungs.

For the individual patient, the story ended well, a 71-year-old man with respiratory failure and sepsis walking out of the hospital after a diagnostic odyssey that conventional tools could not resolve. For the field, the case adds to a mounting body of evidence that the future of severe pneumonia diagnosis is untargeted, sequencing-based, and paired with disciplined clinical interpretation. The technique is not without limitations, including cost, turnaround variability, contamination risk, and the persistent difficulty of distinguishing colonization from infection, but as this report demonstrates, when a patient with bird exposure deteriorates despite seemingly appropriate antibiotics, the answer may be hiding in two organisms at once, and only an unbiased look at the lung’s microbial census will reveal it.

Subject of Research: A case report of severe community-acquired pneumonia involving co-infection with Chlamydia psittaci and ESBL-producing Escherichia coli diagnosed by metagenomic next-generation sequencing.

Article Title: Severe community-acquired pneumonia complicated by co-infection with Chlamydia psittaci and ESBL-producing Escherichia coli: a case report

Article References: Lu, C., Xie, T., Xu, B., Li, Y., & Yurui, Y. (2026). Severe community-acquired pneumonia complicated by co-infection with Chlamydia psittaci and ESBL-producing Escherichia coli: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14001-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14001-2

Keywords: Chlamydia psittaci, psittacosis, community-acquired pneumonia, ESBL-producing Escherichia coli, metagenomic next-generation sequencing, antimicrobial resistance, sepsis, respiratory failure, avian exposure, bronchoalveolar lavage, doxycycline, case report

The patient arrived at the hospital with a low-grade fever and a facial rash, one week after close contact with his daughter, who had been suffering from upper respiratory symptoms. Two years earlier he had been diagnosed with interstitial lung disease, suspected to be bird-related chronic hypersensitivity pneumonitis, a form of inflammatory lung injury driven by exposure to avian antigens such as those from feather duvets and down jackets. His condition had been managed with systemic corticosteroids, which had been carefully tapered and discontinued several months before admission, and he had been rigorously counseled to avoid avian exposures. A former smoker with a 38 pack-year history, he initially received oral levofloxacin from his local physician without improvement, prompting referral to the authors’ hospital.

On admission the clinical picture was deceptively subtle. He was alert, his temperature was 37.0 degrees Celsius, and his oxygen saturation sat at 90 percent on room air while fine crackles could be heard bilaterally and a mild facial rash was visible. Laboratory evaluation showed only mild inflammation, with a C-reactive protein level of 0.89 mg/dL, and importantly, serum KL-6 and surfactant protein D, biomarkers commonly used to track interstitial lung disease activity, remained unchanged from his baseline values. An extensive infectious workup was entirely negative, including serum beta-D-glucan, cytomegalovirus antigenemia, Aspergillus IgG and a multiplex polymerase chain reaction panel for common respiratory pathogens. Given the recent sick contact in the family and the facial rash, clinicians performed parvovirus B19 serology, which returned positive IgM and IgG antibodies, indicating a recent primary infection.

Imaging told a more alarming story. Chest radiography revealed decreased radiolucency in the bilateral middle and lower lung fields compared with films obtained only three months earlier, and high-resolution computed tomography demonstrated newly developed bilateral ground-glass opacities, a finding that in a patient with underlying fibrotic lung disease immediately raises concern for an acute exacerbation. Broad-spectrum antibiotics were started on the assumption of bacterial pneumonia, yet the opacities continued to progress, forcing the team to look deeper. Bronchoscopy was performed, and bronchoalveolar lavage fluid collected from the left B5 segment yielded a total cell count of 1.42 x 10^5 cells per milliliter with striking lymphocytic predominance of 63.5 percent, along with histiocytes at 33.8 percent, neutrophils at 1.0 percent and eosinophils at 1.7 percent.

The decisive result came from molecular testing of that lavage fluid: polymerase chain reaction was positive for parvovirus B19 DNA, directly demonstrating the virus within the lower respiratory tract during the acute phase of illness. Testing for Pneumocystis jirovecii was negative, no pathogenic organisms were isolated in culture, and cytology excluded malignancy. With a compatible exposure history, serologic confirmation of acute infection and viral DNA recovered from the lung itself, the clinicians concluded that the acute respiratory deterioration was associated with parvovirus B19, a diagnosis essentially never made in immunocompetent adults. During hospitalization the serum KL-6 and SP-D levels rose and the patient’s oxygen requirement climbed transiently to 3 liters per minute, reflecting genuine physiologic worsening rather than an incidental imaging finding.

Treatment took the form of high-dose pulsed corticosteroids, with methylprednisolone at 1000 mg per day, which produced rapid clinical and radiological improvement. The patient was transitioned to tapering oral prednisolone and discharged on Day 19 of his admission. At four-month follow-up he remained clinically stable, with sustained resolution of the opacities on serial chest radiographs. The favorable response is notable, though as the authors caution, it does not by itself settle the underlying mechanism, since the suspected bird-related hypersensitivity pneumonitis is generally considered more steroid-responsive than progressive fibrotic diseases such as idiopathic pulmonary fibrosis.

The diagnostic reasoning in this case illuminates a genuine clinical dilemma. Acute exacerbation of interstitial lung disease is defined by rapid respiratory deterioration within one month and the appearance of new bilateral ground-glass opacities on high-resolution computed tomography, criteria that this patient met. Yet distinguishing primary viral pneumonia from infection-triggered acute exacerbation remains notoriously difficult because the two entities overlap substantially in their clinical and radiological features. Previous prospective work cited by the authors detected respiratory viral infections in 19.2 percent of acute exacerbation cases, and such infections are associated with poor short-term outcomes. In this instance, common culprits such as influenza virus and the herpesviruses were excluded, and the absence of any alternative infectious agent or cardiac failure strengthened the case for parvovirus B19 as the causative trigger, although the authors acknowledge that unrecognized avian antigen exposure and progression of the underlying hypersensitivity pneumonitis could not be completely excluded, particularly given the lymphocytic, rather than neutrophilic, lavage profile.

The mechanistic plausibility of parvovirus B19 lung injury rests on well-characterized virology. The virus is a small, non-enveloped, single-stranded DNA virus that enters cells by binding the P antigen, a globoside receptor expressed not only on erythroid progenitors but also on pulmonary endothelial cells. Viral interaction with this receptor may cause endothelial injury, increased vascular permeability and diffuse alveolar damage, the histological substrate of acute lung injury. Experimental studies add a pro-fibrotic dimension: the viral non-structural protein NS1 has been shown to exacerbate fibrotic processes through activation of the TGF-beta/Smad signaling pathway, while the VP1-unique region of the capsid induces inflammatory cytokine release and disrupts epithelial barriers. In a lung already scarred by chronic interstitial disease, these processes could act as a ‘second hit’ that tips a compensated patient into acute exacerbation, providing a coherent biological explanation for what the radiographs and lavage findings captured.

The authors, Tomoki Kishaba and Satoshi Marumo of the Department of Respirology at Kitano Hospital, conclude that although the relative contributions of direct viral lung injury, infection-triggered exacerbation and progression of the underlying bird-related hypersensitivity pneumonitis could not be definitively disentangled, the case highlights the importance of considering parvovirus B19 as a potential contributor to acute respiratory deterioration, particularly in patients with underlying interstitial lung disease. For clinicians, the practical lessons are concrete: a facial rash or known ‘slapped cheek’ contact in an deteriorating ILD patient should prompt parvovirus B19 serology, and bronchoalveolar lavage with viral PCR can identify pathogens that routine respiratory panels miss, since parvovirus B19 does not appear on standard multiplex panels. For virologists and pulmonologists alike, the report underscores how much remains unknown about a virus that infects roughly half of humanity by adulthood, and the authors call for further studies to clarify the mechanisms underlying parvovirus B19-associated pulmonary involvement before such life-threatening presentations are encountered again.

Subject of Research: Acute respiratory deterioration associated with parvovirus B19 infection in a patient with interstitial lung disease.

Article Title: Acute Respiratory Deterioration Following Parvovirus B19 Infection in a Patient With Interstitial Lung Disease: A Case Report

Article References: Kishaba, T., Marumo, S., Nishida, Y., Nohara, E., Higashi, J., Aoki, S., Okura, C., Jinno, S., Tashima, N., Morimoto, C., Kitajima, T., & Inoue, D. (2026). Acute Respiratory Deterioration Following Parvovirus B19 Infection in a Patient With Interstitial Lung Disease: A Case Report. Respirology Case Reports, 14(9), Article e70751. https://doi.org/10.1002/rcr2.70751

Image Credits: AI Generated

DOI: 10.1002/rcr2.70751

Keywords: parvovirus B19, interstitial lung disease, acute exacerbation, hypersensitivity pneumonitis, viral pneumonia, bronchoalveolar lavage, ground-glass opacities, corticosteroids, respiratory infection, lung fibrosis, Acute, Respiratory