Seven Silent Years: When Bronchiectasis Foreshadows a Deadly Autoimmune Disease

A routine cough that refused to go away turned out to be the first visible tremor of a systemic autoimmune storm. In a case report published in Respirology Case Reports, physicians describe a 74-year-old woman whose bronchiectasis—a chronic, irreversible widening of the airways—preceded the diagnosis of ANCA-associated vasculitis by a full seven years. The case, accompanied by a sweeping review of the literature, raises an uncomfortable question for respiratory medicine: how often does an unexplained airway disease quietly announce a vasculitis that nobody thinks to test for until kidneys and skin begin to fail?

ANCA-associated vasculitis, or AAV, is a family of necrotizing small-vessel diseases driven by pathogenic antineutrophil cytoplasmic antibodies. It encompasses microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. Classically, patients present with striking systemic features—rapidly rising creatinine, pulmonary hemorrhage, palpable purpura, peripheral neuropathy—that trigger an immunological workup and serological testing. Bronchiectasis, by contrast, is rarely considered an inaugural manifestation. When it appears in AAV, it is usually interpreted as structural fallout from established vasculitic inflammation rather than a warning shot, a framing that can postpone ANCA testing until organ damage declares itself elsewhere.

The patient at the center of the report arrived in 2018 with a chronic productive cough and a history of intermittent asthma. High-resolution computed tomography revealed focal bronchiectasis confined to the right middle lobe. Her physicians did what good diagnosticians do: they systematically excluded the usual suspects. Serial sputum cultures and bronchoalveolar lavage were negative for bacterial, mycobacterial, and fungal pathogens. Non-tuberculous mycobacterial infection, cystic fibrosis, primary immunodeficiency, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis were all ruled out. Spirometry was normal. Empiric corticosteroids and macrolides were prescribed for presumed non-infective airway inflammation, and her symptoms improved—but never resolved.

Over the following six years, repeat imaging charted a slow, ominous march. The focal right middle lobe disease progressed to multifocal bilateral bronchiectasis, accompanied by tree-in-bud nodularity and mucus plugging, with new parenchymal nodules appearing along the way. Her antinuclear antibody test was negative. Critically, ANCA serology was never obtained, and the diagnosis remained bronchiectasis of undetermined etiology for seven years. The authors of the report are careful not to overclaim causality, but they highlight a stark, narrower fact: seven years elapsed during which an inexpensive blood test that would have reframed the entire diagnosis was never sent.

Then, in 2025, the systemic disease erupted. The woman developed palpable purpura across both lower extremities, hemoptysis, and hematuria. Imaging showed new multifocal bilateral consolidations superimposed on the established bronchiectasis, though without the ground-glass pattern of diffuse alveolar hemorrhage; her hemoglobin and oxygen saturation remained stable and the hemoptysis resolved spontaneously. Her kidneys told a more urgent story. Serum creatinine had surged from 0.46 mg/dL six weeks earlier to 2.09 mg/dL—an estimated glomerular filtration rate collapsing from 100 to 24 mL/min/1.73 m²—and reached a nadir of 2.19 mg/dL on hospital day three, all while urine output remained preserved.

The serology finally caught up with the disease. Indirect immunofluorescence showed a perinuclear pattern, and antigen-specific ELISA confirmed myeloperoxidase-ANCA, or MPO-ANCA, at 250.2 U/mL against a reference value below 1.0, with proteinase 3-ANCA negative. Urinalysis revealed proteinuria with dysmorphic erythrocytes. A renal biopsy sampling fourteen glomeruli showed pauci-immune crescentic glomerulonephritis with a cellular crescent in one glomerulus, no immune deposits, and more than half of the glomeruli intact—Berden focal class, the histological category carrying the most favorable prognosis. Anti-glomerular basement membrane and anti-double-stranded DNA antibodies were negative, and complement was normal. Together, the findings established microscopic polyangiitis.

Treatment followed current guidelines: three days of intravenous methylprednisolone at 500 mg daily, an oral prednisone taper, and rituximab 1 gram repeated after two weeks and then every six months as maintenance, with Pneumocystis prophylaxis. The response was dramatic on the inflammatory front. Within two months her eGFR peaked at 74, stabilizing at 60 at fifteen months—stage 3a chronic kidney disease, a plateau the authors attribute to residual nephron loss after inflammatory suppression. At five months, high-resolution CT showed near-complete resolution of the consolidations, while the underlying bronchiectasis persisted, exactly as expected for fixed structural airway damage. MPO-ANCA fell from 250.2 to 5.2 U/mL by twelve months with documented B-cell depletion, and she remains asymptomatic at fifteen months, her cough finally resolved.

The literature review embedded in the report gives the case its wider significance. A 2024 systematic review and meta-analysis of 24 studies found a pooled bronchiectasis prevalence of 19 percent in AAV—higher with MPO-ANCA than PR3-ANCA, at 28 percent versus 13 percent—and noted that bronchiectasis may precede, coincide with, or follow the vasculitis. One retrospective cohort of 58 AAV patients found bronchiectasis in 37.9 percent, all MPO-ANCA positive, independently associated with MPO specificity, female sex, and age at diagnosis. Most striking is a multicentre cohort of 61 patients with AAV and bronchiectasis: in 25 of them, bronchiectasis preceded the vasculitis by a median of 16 years, and this bronchiectasis-first group had more microscopic polyangiitis, more MPO-ANCA, and shorter survival. The present patient—female, MPO-positive, with airway disease antedating systemic vasculitis by seven years—fits that phenotype precisely.

Yet the authors resist a simple causal narrative, and the evidence supports their caution. Where bronchiectasis was universally MPO-associated, affected patients actually had less frequent renal involvement than those without it, and bronchiectasis in AAV generally does not respond to immunosuppression—consistent with this patient, whose consolidations melted away while the structural airway disease remained. Whether earlier serology would have changed her outcome is genuinely uncertain. The real gap, they argue, lies in the current diagnostic algorithms. The 2025 European Respiratory Society guideline strongly recommends standardized testing for the underlying cause of bronchiectasis, but ANCA appears only within an etiological algorithm gated behind systemic features—coexisting autoimmune disease, hemoptysis, or signs of vasculitis—and the guideline explicitly states these components are not separate recommendations. A 2025 observational study screening 468 bronchiectasis patients found ANCA positivity in just 3.8 percent and concluded screening should remain individualized. The 2026 American College of Chest Physicians guideline addresses management only. This patient had none of the trigger features before 2025: her gap sits outside current algorithms—culture-negative, radiographically progressive, incompletely corticosteroid-responsive disease without systemic features.

One diagnostic alternative deserved careful exclusion. The combination of MPO-ANCA positivity, long-standing airway disease, and a history of asthma raises eosinophilic granulomatosis with polyangiitis as the leading rival. Applying the 2022 ACR/EULAR classification criteria is instructive: her cumulative score was just 2 points—3 for obstructive airway disease, credited on her asthma history despite normal spirometry, minus 1 for hematuria—far below the 6 required, because the most heavily weighted item, a maximum eosinophil count of at least 1 × 10⁹ per liter, was never met. Eosinophils were 0 percent at presentation and had never been elevated; total IgE, measured in 2024, was 114 kU/L without the marked elevation characteristic of EGPA. Pauci-immune crescentic glomerulonephritis with markedly elevated MPO-ANCA and no tissue or blood eosinophilia settles the question in favor of microscopic polyangiitis. The case also carries a technical lesson in serology: the discordance between her falling MPO-ANCA titers and persistent weak immunofluorescence positivity is compatible with non-MPO perinuclear antibodies during B-cell depletion, reinforcing guidance against basing treatment decisions on titers alone. Limitations remain—alveolar hemorrhage was never definitively confirmed, and the absence of ANCA testing during the airway phase means the timing of seroconversion is unknown. What endures is the clinical message: in a patient with progressive, culture-negative bronchiectasis that resists the usual treatments, the vasculitis may already be knocking, years before the door gives way.

Subject of Research: Bronchiectasis as an early sentinel manifestation of ANCA-associated vasculitis

Article Title: Bronchiectasis as the Sentinel Manifestation of ANCA‐Associated Vasculitis: A Case Report and Literature Review

Article References: Kim, A., Vartany, C., Hegde, S., Lau, K., Tatosyan, L., & Liang, B. (2026). Bronchiectasis as the Sentinel Manifestation of ANCA ‐Associated Vasculitis: A Case Report and Literature Review. Respirology Case Reports, 14(10), Article e70777. https://doi.org/10.1002/rcr2.70777

Image Credits: AI Generated

DOI: 10.1002/rcr2.70777

Keywords: bronchiectasis, ANCA-associated vasculitis, microscopic polyangiitis, MPO-ANCA, case report, glomerulonephritis, rituximab, high-resolution CT, EGPA, clinical guidelines, autoimmune screening, respiratory medicine