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Next Generation NCLEX Case Study Sample Questions

One of the big changes on the Next Generation NCLEX exam is a shift toward case studies. Case studies often require a deeper level of critical thinking, and understanding diseases on a more in-depth level (especially the pathophysiology) will make these types of questions easier to answer.

In this article, you’ll be able to watch a free video to help you prepare for the new Next Generation NCLEX case study format. Nurse Sarah will walk you step-by-step through each scenario and help you understand how to use critical thinking and nursing knowledge to answer these types of questions.

Next Generation NCLEX Case Study Review Questions Video

NGN Case Study Sample Questions and Answers

First, let’s take a look at our case study summary below:

Case Study Summary:

A 68-year-old male is admitted with shortness of breath. He reports difficulty breathing with activity, lying down, or while sleeping. He states that in order to “breathe easier,” he has had to sleep in a recliner for the past week. The patient has a history of hypertension, myocardial infarction (2 years ago), and cholecystectomy (10 years ago). The patient is being transferred to a cardiac progressive care unit for further evaluation and treatment.

Question 1 of 6: The nurse receives the patient admitted with shortness of breath. What findings are significant and require follow-up? The options are listed below. Select all that apply.

To answer this first question in the NGN case study, let’s look at the information provided in the nursing notes and vital signs tabs provided:

This question is asking us to identify findings that are significant and require the nurse to follow-up. In other words, what is presenting that we can’t ignore but need to investigate further.

Therefore, let’s comb through the nursing notes and vital signs to see what is abnormal and requires follow-up.

First, the patient arrived to the room via stretcher. That’s fine and doesn’t necessarily require follow-up.

Next, the patient is alert and oriented x 4 (person, place, time, event). This tells us that the patient’s neuro status is intact so far. Therefore, the shortness of breath isn’t affecting the patient’s mental function yet (we have enough oxygen on board right now for brain activity).

However, the nurse has noticed the shortness of breath with activity and talking, which should not normally happen. This tells us something is wrong and is significant enough to require follow-up. We want to know why is this happening, is it going to get worse, etc.

The patient’s weight and vital signs were collected (this is good). Weight is 155 lbs. and BMI is within a healthy range (doesn’t tell us too much but may be useful later). The patient is also connected to a bedside monitor, so they need to be monitored constantly like on a progressive care unit.

The monitor shows sinus tachycardia . This is significant because it seems the patient’s shortness of breath is causing the heart to compensate by increasing the heart rate to provide more oxygen (hence the lungs may be compromised).

Then we find out that the lungs are indeed compromised because crackles are heard in both lungs , and this may be why our patient is short of breath. This is significant (could the patient have pulmonary edema?)

Then we find out the nurse has noted an S3. This is an extra heart sound noted after S2. And what jumps out to me about this is that it is usually associated with volume overload in the heart like in cases of heart failure . However, S3 may be normal in some people under 40 or during pregnancy, but that’s not the case with our patient based on what we read in the case summary.

Therefore, based on everything I’m reading in this case study, I’m thinking this patient may have heart failure, but we need those test results back (especially the echo and chest x-ray, and hopefully a BNP will be in there too).

We are also told that the patient has an 18 gauge IV inserted (which is good thing to have so we can give medications if required), orders have been received, labs drawn, and testing results are pending.

Now let’s look at the “Vital Signs” tab above, and ask yourself what is normal vs. abnormal for this patient (adult male).

• The heart rate is high at 112 (tachycardia), and should normally be 60-100 bpm (see heart rhythms ).
• Blood pressure is higher than normal (normal is 120/80), which indicates hypertension.
• Oxygen saturation is 94% (this is on the low side as we’d normally want around 95% or higher, and the patient is on 4 L nasal cannula, which tells us the lungs are not okay).
• Respiratory rate is increased (26 breaths per minute)…normal is 12-20 breaths per minute.

Based on the information we were provided, I’ve selected the answers below. These findings are significant and definitely require follow-up by the nurse.

When answering these NGN case study questions, it’s helpful to think of the ABCDE (airway, breathing, circulation, etc.) as all of these fall into that category. If we don’t follow-up on the shortness of breath, crackles, respiratory rate, o2 saturation (94% on 4 L nasal cannula), the respiratory system can further decline.

In addition, the sinus tachycardia, S3 gallop, and hypertension could indicate fluid overload in the heart. This may cause the heart to tire out and lead the lethal rhythm. On the other hand, temperature, pain, weight, and BMI are not abnormal and do not require follow-up.

See the Complete Next Generation NCLEX Case Study Review

Each question in the case study builds on the previous question. To see how these questions evolve based on the patient’s condition and labs, watch the entire Next Generation NCLEX Case Study Review video on our YouTube Channel (RegisteredNurseRN).

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Case study: 60-year-old female presenting with shortness of breath.

Deepa Rawat ; Sandeep Sharma .

Affiliations

Last Update: February 20, 2023 .

• Case Presentation

The patient is a 60-year-old white female presenting to the emergency department with acute onset shortness of breath.  Symptoms began approximately 2 days before and had progressively worsened with no associated, aggravating, or relieving factors noted. She had similar symptoms approximately 1 year ago with an acute, chronic obstructive pulmonary disease (COPD) exacerbation requiring hospitalization. She uses BiPAP ventilatory support at night when sleeping and has requested to use this in the emergency department due to shortness of breath and wanting to sleep.

She denies fever, chills, cough, wheezing, sputum production, chest pain, palpitations, pressure, abdominal pain, abdominal distension, nausea, vomiting, and diarrhea.

She reports difficulty breathing at rest, forgetfulness, mild fatigue, feeling chilled, requiring blankets, increased urinary frequency, incontinence, and swelling in her bilateral lower extremities that are new-onset and worsening. Subsequently, she has not ambulated from bed for several days except to use the restroom due to feeling weak, fatigued, and short of breath.

There are no known ill contacts at home. Her family history includes significant heart disease and prostate malignancy in her father. Social history is positive for smoking tobacco use at 30 pack years. She quit smoking 2 years ago due to increasing shortness of breath. She denies all alcohol and illegal drug use. There are no known foods, drugs, or environmental allergies.

Past medical history is significant for coronary artery disease, myocardial infarction, COPD, hypertension, hyperlipidemia, hypothyroidism, diabetes mellitus, peripheral vascular disease, tobacco usage, and obesity.  Past surgical history is significant for an appendectomy, cardiac catheterization with stent placement, hysterectomy, and nephrectomy.

Her current medications include fluticasone-vilanterol 100-25 mcg inhaled daily, hydralazine 50 mg by mouth, 3 times per day, hydrochlorothiazide 25 mg by mouth daily, albuterol-ipratropium inhaled every 4 hours PRN, levothyroxine 175 mcg by mouth daily, metformin 500 mg by mouth twice per day, nebivolol 5 mg by mouth daily, aspirin 81 mg by mouth daily, vitamin D3 1000 units by mouth daily, clopidogrel 75 mg by mouth daily, isosorbide mononitrate 60 mg by mouth daily, and rosuvastatin 40 mg by mouth daily.

Physical Exam

Initial physical exam reveals temperature 97.3 F, heart rate 74 bpm, respiratory rate 24, BP 104/54, HT 160 cm, WT 100 kg, BMI 39.1, and O2 saturation 90% on room air.

Constitutional:  Extremely obese, acutely ill-appearing female. Well-developed and well-nourished with BiPAP in place. Lying on a hospital stretcher under 3 blankets.

HEENT: 

• Head: Normocephalic and atraumatic
• Mouth: Moist mucous membranes 
• Macroglossia
• Eyes: Conjunctiva and EOM are normal. Pupils are equal, round, and reactive to light. No scleral icterus. Bilateral periorbital edema present.
• Neck: Neck supple. No JVD present. No masses or surgical scarring. 
• Throat: Patent and moist

Cardiovascular:  Normal rate, regular rhythm, and normal heart sound with no murmur. 2+ pitting edema bilateral lower extremities and strong pulses in all four extremities.

Pulmonary/Chest:  No respiratory status distress at this time, tachypnea present, (+) wheezing noted, bilateral rhonchi, decreased air movement bilaterally. The patient was barely able to finish a full sentence due to shortness of breath.

Abdominal:  Soft. Obese. Bowel sounds are normal. No distension and no tenderness

Skin: Skin is very dry

Neurologic: Alert, awake, able to protect her airway. Moving all extremities. No sensation losses

• Initial Evaluation

Initial evaluation to elucidate the source of dyspnea was performed and included CBC to establish if an infectious or anemic source was present, CMP to review electrolyte balance and review renal function, and arterial blood gas to determine the PO2 for hypoxia and any major acid-base derangement, creatinine kinase and troponin I to evaluate the presence of myocardial infarct or rhabdomyolysis, brain natriuretic peptide, ECG, and chest x-ray. Considering that it is winter and influenza is endemic in the community, a rapid influenza assay was obtained as well.

Largely unremarkable and non-contributory to establish a diagnosis.

Showed creatinine elevation above baseline from 1.08 base to 1.81, indicating possible acute injury. EGFR at 28 is consistent with chronic renal disease. Calcium was elevated to 10.2. However, when corrected for albumin, this corrected to 9.8 mg/dL. Mild transaminitis is present as seen in alkaline phosphatase, AST, and ALT measurements which could be due to liver congestion from volume overload.

Initial arterial blood gas with pH 7.491, PCO2 27.6, PO2 53.6, HCO3 20.6, and oxygen saturation 90% on room air, indicating respiratory alkalosis with hypoxic respiratory features.

Creatinine kinase was elevated along with serial elevated troponin I studies. In the setting of her known chronic renal failure and acute injury indicated by the above creatinine value, a differential of rhabdomyolysis is determined.

Influenza A and B: Negative

Normal sinus rhythm with non-specific ST changes in inferior leads. Decreased voltage in leads I, III, aVR, aVL, aVF.

Chest X-ray

Findings: Bibasilar airspace disease that may represent alveolar edema. Cardiomegaly noted. Prominent interstitial markings were noted. Small bilateral pleural effusions

Radiologist Impression: Radiographic changes of congestive failure with bilateral pleural effusions greater on the left compared to the right

• Differential Diagnosis
• Acute on chronic COPD exacerbation
• Acute on chronic renal failure
• Bacterial pneumonia
• Congestive heart failure
• Pericardial effusion
• Hypothyroidism
• Influenza pneumonia
• Pulmonary edema
• Pulmonary embolism
• Confirmatory Evaluation

On the second day of the admission patient’s shortness of breath was not improved, and she was more confused with difficulty arousing on conversation and examination. To further elucidate the etiology of her shortness of breath and confusion, the patient's husband provided further history. He revealed that she is poorly compliant with taking her medications. He reports that she “doesn’t see the need to take so many pills.”

Testing was performed to include TSH, free T4, BNP, repeated arterial blood gas, CT scan of the chest, and echocardiogram. TSH and free T4 evaluate hypothyroidism. BNP evaluates fluid load status and possible congestive heart failure. CT scan of the chest will look for anatomical abnormalities. An echocardiogram is used to evaluate left ventricular ejection fraction, right ventricular function, pulmonary artery pressure, valvular function, pericardial effusion, and any hypokinetic area.

• TSH: 112.717 (H)
• Free T4: 0.56 (L)
• TSH and Free T4 values indicate severe primary hypothyroidism. 

BNP can be falsely low in obese patients due to the increased surface area. Additionally, adipose tissue has BNP receptors which augment the true BNP value. Also, African American patients with more excretion may have falsely low values secondary to greater excretion of BNP. This test is not that helpful in renal failure due to the chronic nature of fluid overload. This allows for desensitization of the cardiac tissues with a subsequent decrease in BNP release.

Repeat arterial blood gas on BiPAP ventilation shows pH 7.397, PCO2 35.3, PO2 72.4, HCO3 21.2, and oxygen saturation 90% on 2 L supplemental oxygen.

CT chest without contrast was primarily obtained to evaluate the left hemithorax, especially the retrocardiac area.

Radiologist Impression: Tiny bilateral pleural effusions. Pericardial effusion. Coronary artery calcification. Some left lung base atelectasis with minimal airspace disease.

Echocardiogram

The left ventricular systolic function is normal. The left ventricular cavity is borderline dilated.

The pericardial fluid is collected primarily posteriorly, laterally but not apically. There appeared to be a subtle, early hemodynamic effect of the pericardial fluid on the right-sided chambers by way of an early diastolic collapse of the RA/RV and delayed RV expansion until late diastole. A dedicated tamponade study was not performed. 

The estimated ejection fraction appears to be in the range of 66% to 70%. The left ventricular cavity is borderline dilated.

The aortic valve is abnormal in structure and exhibits sclerosis.

The mitral valve is abnormal in structure. Mild mitral annular calcification is present. There is bilateral thickening present. Trace mitral valve regurgitation is present.

• Myxedema coma or severe hypothyroidism
• Pericardial effusion secondary to myxedema coma
• COPD exacerbation
• Acute on chronic hypoxic respiratory failure
• Acute respiratory alkalosis
• Bilateral community-acquired pneumonia
• Small bilateral pleural effusions
• Acute mild rhabdomyolysis
• Acute chronic, stage IV, renal failure
• Elevated troponin I levels, likely secondary to Renal failure 
• Diabetes mellitus type 2, non-insulin-dependent
• Extreme obesity
• Hepatic dysfunction

The patient was extremely ill and rapidly decompensating with multisystem organ failure, including respiratory failure, altered mental status, acute on chronic renal failure, and cardiac dysfunction. The primary concerns for the stability of the patient revolved around respiratory failure coupled with altered mental status. In the intensive care unit (ICU), she rapidly began to fail BiPAP therapy. Subsequently, the patient was emergently intubated in the ICU.  A systemic review of therapies and hospital course is as follows:

Considering the primary diagnosis of myxedema coma, early supplementation with thyroid hormone is essential. Healthcare providers followed the American Thyroid Association recommendations, which recommend giving combined T3 and T4 supplementation; however, T4 alone may also be used. T3 therapy is given as a bolus of 5 to 20 micrograms intravenously and continued at 2.5 to 10 micrograms every 8 hours. An intravenous loading dose of 300 to 600 micrograms of T4 is followed by a daily intravenous dose of 50 to 100 micrograms. Repeated monitoring of TSH and T4 should be performed every 1 to 2 days to evaluate the effect and to titrate the dose of medication. The goal is to improve mental function. Until coexistent adrenal insufficiency is ruled out using a random serum cortisol measurement, 50 to 100 mg every 8 hours of hydrocortisone should be administered. In this case, clinicians used hydrocortisone 100 mg IV every 8 hours. Dexamethasone 2 to 4 mg every 12 hours is an alternative therapy.

The patient’s mental status rapidly worsened despite therapy. In the setting of her hypothyroidism history, this may be myxedema coma or due to the involvement of another organ system. The thyroid supplementation medications and hydrocortisone were continued. A CT head without contrast was normal.

Respiratory

For worsening metabolic acidosis and airway protection, the patient was emergently intubated. Her airway was deemed high risk due to having a large tongue, short neck, and extreme obesity. As the patient’s heart was preload dependent secondary to pericardial effusion, a 1-liter normal saline bolus was started. Norepinephrine was started at a low dose for vasopressor support, and ketamine with low dose Propofol was used for sedation. Ketamine is a sympathomimetic medication and usually does not cause hypotension as all other sedatives do. The patient was ventilated with AC mode of ventilation, tidal volume of 6 ml/kg ideal body weight, flow 70, initial fio2 100 %, rate 26 per minute (to compensate for metabolic acidosis), PEEP of 8.

Cardiovascular

She was determined to be hemodynamically stable with a pericardial effusion. This patient’s cardiac dysfunction was diastolic in nature, as suggested by an ejection fraction of 66% to 70%. The finding of posterior pericardial effusion further supported this conclusion. The posterior nature of this effusion was not amenable to pericardiocentesis. As such, this patient was preload dependent and showed signs of hypotension. The need for crystalloid fluid resuscitation was balanced against the impact increased intravascular volume would have on congestive heart failure and fluid overload status. Thyroid hormone replacement as above should improve hypotension. However, vasopressor agents may be used to maintain vital organ perfusion targeting a mean arterial pressure of greater than 65 mm Hg as needed. BP improved after fluid bolus, and eventually, the norepinephrine was stopped. Serial echocardiograms were obtained to ensure that the patient did not develop tamponade physiology. Total CK was elevated, which was likely due to Hypothyroidism compounded with chronic renal disease.

Infectious Disease

Blood cultures, urine analysis, and sputum cultures were obtained. The patient's white blood cell count was normal. This is likely secondary to her being immunocompromised due to hypothyroidism and diabetes. In part, the pulmonary findings of diffuse edema and bilateral pleural effusions can be explained by cardiac dysfunction. Thoracentesis of pleural fluid was attempted, and the fluid was analyzed for cytology and gram staining to rule out infectious or malignant causes as both a therapeutic and diagnostic measure. Until these results return, broad-spectrum antibiotics are indicated and may be discontinued once the infection is ruled out completely.

Gastrointestinal

Nasogastric tube feedings were started on the patient after intubation. She tolerated feedings well. AST and ALT were mildly elevated, which was thought to be due to hypothyroidism, and as the TSH and free T4 improved, her AST and ALT improved. Eventually, these values became normal once her TSH level was close to 50.

Her baseline creatinine was found to be close to 1.08 in prior medical records. She presented with a creatinine of 1.8 in the emergency department. Since hypothyroidism causes fluid retention in part because thyroid hormone encourages excretion of free water and partly due to decreased lymphatic function in returning fluid to vascular circulation.  Aggressive diuresis was attempted. As a result, her creatinine increased initially but improved on repeated evaluation, and the patient had a new baseline creatinine of 1.6. Overall she had a net change in the fluid status of 10 liters negative by her ten days of admission in the ICU.

Mildly anemic otherwise, WBC and platelet counts were normal. Electrolyte balance should be monitored closely, paying attention to sodium, potassium, chloride, and calcium specifically as these are worsened in both renal failure and myxedema. 

Daily sedation vacations were enacted, and the patient's mental status improved and was much better when TSH was around 20. The bilateral pleural effusions improved with aggressive diuresis. Breathing trials were initiated when the patient's fio2 requirements decreased to 60% and a PEEP of 8. She was eventually extubated onto BiPAP and then high-flow nasal cannula while off of BiPAP. Pericardial fluid remained stable, and no cardiac tamponade pathology developed. As a result, it was determined that a pericardial window was unnecessary. Furthermore, she was not a candidate for pericardiocentesis as the pericardial effusion was located posterior to the heart. Her renal failure improved with improved cardiac function, diuretics, and thyroid hormone replacement.

After extubation patient had speech and swallow evaluations and was able to resume an oral diet. The patient was eventually transferred out of the ICU to the general medical floor and eventually to a rehabilitation unit.

Despite the name myxedema coma, most patients will not present in a coma status. This illness is at its core a severe hypothyroidism crisis that leads to systemic multiorgan failure. Thyroid hormones T3, and to a lesser extent, T4 act directly on a cellular level to upregulate all metabolic processes in the body. Therefore, deficiency of this hormone is characterized by systemic decreased metabolism and decreased glucose utilization along with increased production and storage of osmotically active mucopolysaccharide protein complexes into peripheral tissues resulting in diffuse edema and swelling of tissue. [1]

Myxedema coma is an illness that occurs primarily in females at a rate of 4:1 compared to men. It typically impacts the elderly at the age of greater than 60 years old, and approximately 90% of cases occur during the winter months. Myxedema coma is the product of longstanding unidentified or undertreated hypothyroidism of any etiology. Thyroid hormone is necessary throughout the body and acts as a regulatory hormone that affects many organ systems. [2] In cardiac tissues, myxedema coma manifests as decreased contractility with subsequent reduction in stroke volume and overall cardiac output.  Bradycardia and hypotension are typically present also. Pericardial effusions occur due to the accumulation of mucopolysaccharides in the pericardial sac, which leads to worsened cardiac function and congestive heart failure from diastolic dysfunction. Capillary permeability is also increased throughout the body leading to worsened edema. Electrocardiogram findings may include bradycardia and low-voltage, non-specific ST waveform changes with possible inverted T waves.

Neurologic tissues are impacted in myxedema coma leading to the pathognomonic altered mental status resulting from hypoxia and decreased cerebral blood flow secondary to cardiac dysfunction as above. Additionally, hypothyroidism leads to decreased glucose uptake and utilization in neurological tissue, thus worsening cognitive function.

The pulmonary system typically manifests this disease process through hypoventilation secondary to the central nervous system (CNS) depression of the respiratory drive with blunting of the response to hypoxia and hypercapnia. Additionally, metabolic dysfunction in the muscles of respiration leads to respiratory fatigue and failure, macroglossia from mucopolysaccharide driven edema of the tongue leads to mechanical obstruction of the airway, and obesity hypoventilation syndrome with the decreased respiratory drive as most hypothyroid patients suffer from obesity.

Renal manifestations include decreased glomerular filtration rate from the reduced cardiac output and increased systemic vascular resistance coupled with acute rhabdomyolysis lead to acute kidney injury. In the case of our patient above who has a pre-existing renal disease status post-nephrectomy, this is further worsened.  The net effect is worsened fluid overload status compounding the cardiac dysfunction and edema. [3]

The gastrointestinal tract is marked by mucopolysaccharide-driven edema as well leading to malabsorption of nutrients, gastric ileus, and decreased peristalsis. Ascites is common because of increased capillary permeability in the intestines coupled with coexistent congestive heart failure and congestive hepatic failure. Coagulopathies are common to occur as a result of this hepatic dysfunction.

Evaluation: The diagnosis of myxedema coma, as with all other diseases, is heavily reliant on the history and physical exam. A past medical history including hypothyroidism is highly significant whenever decreased mental status or coma is identified. In the absence of identified hypothyroidism, myxedema coma is a diagnosis of exclusion when all other sources of coma have been ruled out. If myxedema coma is suspected, evaluation of thyroid-stimulating hormone (TSH), free thyroxine (T4), and serum cortisol is warranted. T4 will be extremely low. TSH is variable depending on the etiology of hypothyroidism, with a high TSH indicating primary hypothyroidism and a low or normal TSH indicating secondary etiologies. Cortisol may be low indicating adrenal insufficiency because of hypothyroidism.  [4]

Prognosis: Myxedema coma is a medical emergency. With proper and rapid diagnosis and initiation of therapy, the mortality rate is still as high as 25% to 50%. The most common cause of death is due to respiratory failure. The factors which suggest a poorer prognosis include increased age, persistent hypothermia, bradycardia, low score Glasgow Coma Scale, or multi-organ impairment indicated by high APACHE (Acute Physiology and Chronic Health Evaluation) II score. For these reasons, placement in an intensive care unit with a low threshold for intubation and mechanical ventilation can improve mortality outcomes. [3] [5]

• Pearls of Wisdom
• Not every case of shortness of breath is COPD or congestive heart failure (CHF). While less likely, a history of hypothyroidism should raise suspicion of myxedema coma in a patient with any cognitive changes.
• Myxedema is the great imitator illness that impacts all organ systems. It can easily be mistaken for congestive heart failure, COPD exacerbation, pneumonia, renal injury or failure, or neurological insult.
• Initial steps in therapy include aggressive airway management, thyroid hormone replacement, glucocorticoid therapy, and supportive measures.
• These patients should be monitored in an intensive care environment with continuous telemetry. [6]
• Enhancing Healthcare Team Outcomes

This case demonstrates how all interprofessional healthcare team members need to be involved in arriving at a correct diagnosis, particularly in more challenging cases such as this one. Clinicians, specialists, nurses, pharmacists, laboratory technicians all bear responsibility for carrying out the duties pertaining to their particular discipline and sharing any findings with all team members. An incorrect diagnosis will almost inevitably lead to incorrect treatment, so coordinated activity, open communication, and empowerment to voice concerns are all part of the dynamic that needs to drive such cases so patients will attain the best possible outcomes.

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Case Study of 60 year old female presenting with Shortness of Breath Contributed by Sandeep Sharma, MD

Disclosure: Deepa Rawat declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Rawat D, Sharma S. Case Study: 60-Year-Old Female Presenting With Shortness of Breath. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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• Open access
• Published: 10 April 2024

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease

• François Lestelle 1 ,
• Catherine Beigelman 2 ,
• David Rotzinger 2 ,
• Salim Si-Mohamed 3 ,
• Mouhamad Nasser 1 ,
• Lidwine Wemeau 4 ,
• Sandrine Hirschi 5 ,
• Grégoire Prevot 6 ,
• Antoine Roux 7 ,
• Vincent Bunel 8 ,
• Emmanuel Gomez 9 ,
• Laurent Sohier 10 ,
• Helene Morisse Pradier 11 ,
• Martine Reynaud Gaubert 12 ,
• Anne Gondouin 13 ,
• Romain Lazor 14 ,
• Jean-Charles Glerant 15 ,
• Françoise Thivolet Bejui 16 ,
• Magali Colombat 17 ,
• Vincent Cottin 1 , 18 &

the OrphaLung network

Respiratory Research volume  25 , Article number:  159 ( 2024 ) Cite this article

238 Accesses

18 Altmetric

Metrics details

Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs.

Study design and methods

A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry.

Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean ( ±  SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 ( p  = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation ( p  = 0.005).

Conclusions

Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Take-home message

Diffuse pulmonary light chain deposition disease is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and diffusion capacity impairment, and poor outcome.

Plain language summary

Diffuse pulmonary light chain deposition disease is an exceedingly rare disease of the lungs, whereby parts of abnormal antibodies (proteins involved in host defense especially against microorganisms) deposit in the lungs. This disease is characterised by a peculiar pattern on chest CT, with dilation of bronchi and formation of air-filled cysts (holes), and progresses in several years to chronic respiratory insufficiency.

Immunoglobulins can cause specific forms of lung involvement. Their physiochemical properties and size are important pathogenetic determinants. Two forms of immunoglobulin light chains (LC) can be deposited in tissues: amyloid [ 1 ] and non-amyloid. Light chain deposition disease (LCDD) is a term restricted to the non-amyloid forms of LC deposition.

LCDD is a rare multisystemic entity described by Randall in 1976 [ 2 ] as the deposition of a nonfibrillary, amorphous material that does not have a β-pleated sheet configuration and consequently does not bind Congo red nor have apple-green birefringence with Congo red stain. Contrary to LC amyloidosis [ 3 ], LCDD is mostly composed of kappa LC. Moreover, electronic microscopy does not show a fibrillary pattern but electron-dense granular deposits along basement membranes [ 4 ]. The diagnosis of LCDD is established by immunohistological analysis of affected organs. It requires a formalin-fixed paraffin-embedded sample for microscopic examination and a frozen sample for immunofluorescence analysis with anti-kappa and anti-lambda antibodies. When a frozen tissue sample is not available, mass spectrometry on formalin-fixed paraffin-embedded tissue can be used [ 5 ].

Clinical manifestations of LCDD vary according to the organs involved. Lung involvement appears to be very uncommon but may be underrecognised especially when the deposition of LCs is limited to the lung. Since its first report in 1988 [ 6 ], pulmonary LCDD has been described as either nodular or diffuse [ 7 , 8 ]. The nodular form is generally seen in patients who have no evidence of plasma cell dyscrasia. Diffuse LCDD is characterised by parenchymal cysts, or airway involvement [ 9 , 10 ] including bronchiectasis [ 11 ]. Pathologically, diffuse LCDD is characterised by LC deposits along the basement membranes of the alveolar, bronchial, and vascular walls. The putative pathophysiology of cyst formation involves the degradation of elastic fibers by matrix metalloproteinases [ 12 ].

The clinical symptoms reported in previous studies are chest discomfort, haemoptysis, and progressive dyspnea leading to chronic respiratory failure [ 13 , 14 , 15 ]. Although no treatment is validated, chemotherapy is often prescribed to control monoclonal LC secretion in the serum [ 16 ]. Lung transplantation may be performed [ 17 ].

Data on pulmonary LCDD are scarce and limited to small series or case reports. The main objectives of this study were to: 1) describe the clinical, functional and radiological characteristics at presentation, 2) determine lung function during follow-up and estimate time to transplantation or death.

Patient selection and data collection

This retrospective multicentre study was conducted in the French OrphaLung network, a cooperative group of lung specialists. Patient data regarding clinical, laboratory, functional, radiological characteristics, and outcome were collected using a case report form. Patients were considered eligible if the diagnosis of pulmonary LCDD was confirmed by immunohistochemistry. The exclusion criteria were uncertain diagnosis, solitary pulmonary nodules, and predominance of amyloid deposits.

Ethical consideration

This study was conducted with respect to the Declaration of Helsinki. It was approved by the ethics committee of the Hospices Civils de Lyon and was registered with the national data protection agency (Commission Nationale de l’Informatique et des Libertés, number 20–075). According to the legislation in place at the time of the study, informed consent signature was waived, but each patient was informed by a written letter and could object to the use of their personal data. Several patients were reported in previous publications [ 10 , 11 , 12 , 14 , 17 , 18 ].

Pulmonary function tests

Lung volumes were measured by plethysmography, and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) by flow–volume curve, using GLI reference equations. Carbon monoxide transfer factor (DLco) was assessed with the single-breath method. Hypoxemia was defined as a partial pressure of oxygen in arterial blood (PaO2) < 80 mmHg.

Chest computed tomography (CT)

Two expert chest radiologists (SSM, DR) blinded to the clinical data reviewed the baseline and latest available computed tomography (CT) images during follow-up and before lung transplantation. If consensus was not obtained, a third expert radiologist (CB) settled the description. A CT grading system was used to document cyst number, size of the largest cyst, shape (round, oval, irregular), internal septation, and distribution. Bronchiectases were classified by their appearance (cylindric, varicose, cystic), their proximal or distal distribution, and the presence of bronchial wall thickening. Then, based on imaging, the predominant imaging pattern was classified as bronchiectatic, cystic, or mixed. To evaluate temporal changes in imaging findings, the last available follow-up CT was compared to the baseline CT.

Pathological assessment

Histology reports of lung biopsies were collected and centrally reviewed by an expert pathologist in the field (MC) to confirm the diagnosis of LCDD, using previously described criteria [ 5 ], i.e. biopsies had to stain negative with Congo red and demonstrate LC deposits on frozen tissue under immunofluorescence microscopy. When frozen tissue was unavailable, mass spectrometry was used for diagnostic confirmation [ 19 ].

Statistical analysis

Although normal distribution could not be assumed due to the small sample size and the expected heterogeneity in disease behavior, Shapiro–Wilk test was used to check for normal and skewed distributions. Non-parametric tests were used in the absence of normality. Continuous variables are presented as means (percentages) ± standard deviation (SD) or as median (range).

The Wilcoxon signed-rank test was applied to compare pre- and post-treatment lung function decline, and the Mann–Whitney U test was used to compare measures between groups. Chi-squared test, Fisher’s exact test and Student’s t test were used where appropriate. For each patient, the estimated annual decline rate in DLCO and FEV1 expressed in %/year and in mL/year, respectively, were calculated by linear regression. The average ∆FEV1 and ΔDLCO were calculated in patients who had completed a minimum of 24 months of follow-up and a minimum of four measures. Event-free survival, defined as the time from the first consultation to transplantation or death from any cause, was estimated using the Kaplan–Meier survival method, and univariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals.

Statistical significance was set at p  < 0.05 (two-tailed). IBM SPSS Statistics for Windows, Version 25.0. (IBM Corp, Armonk, NY) and RStudio (v1.3.959) were used for statistical analyses.

Baseline characteristics

Out of 61 patients identified between 1998 and 2020 in 12 French centres and one Swiss centre, 31 met the eligibility criteria and were included in the analysis (Figure S 1 ). Overall, 68% of patients were women and the mean ± SD age at diagnosis was 50 ± 10.7 years. The median (range) interval between the onset of symptoms and diagnosis was 4 (1–30) years. Twenty (67%) patients were current or former smokers with a median of 23.8 (2.5–120) pack-years. All patients except two had dyspnea (Table  1 ).

At baseline, FEV1/FVC was < 0.70 in 45% of patients. FEV1 was lower than 80% of the predicted value in 43% of patients. DLCO was 52 ± 24% (Table  1 ). Hypoxemia was present in 68% of patients.

Haematological characteristics and biology

Bone marrow biopsy or aspiration performed in 21 cases showed > 10% of plasma cells in three patients. A bone marrow B-cell clone search was performed in seven cases and was found in four. Immunofixation identified a circulating monoclonal component as IgM in 52% of cases. Kappa/lambda ratio of serum LC was increased in 21 patients. Free monoclonal kappa LC was increased in the serum of 21/23 patients with a mean level of 236.2 ( ±  344.4) mg/L (Table  1 ). An auto immune workup, including antinuclear and antineutrophilic cytoplasmic antibodies, performed in 22 patients, was negative in all but one patient with anti-SSA and anti-SSB antibodies.

Histology and immunohistochemistry

The most frequently used method to obtain tissue was videothoracoscopic lung biopsy (36%) (Figure S 2 A). The pathological examination of lung biopsies demonstrated cystic destruction and bronchiolar dilatation in all cases (Figure S 2 B). In all patients, biopsy specimens showed Congo red negative eosinophilic deposits infiltrating alveolar walls, small airways, and/or vessels. Immunofluorescence assay of frozen tissues was performed in 25 cases, showing LC deposition stained using anti-kappa antibodies in 19 patients, as illustrated in Figure S 2 C. In contrast, anti-lambda antibody staining confirmed the diagnosis in only one patient. Electron microscopy, performed in five patients, revealed granular dense electron deposits in all cases. Mass spectrometry-based analysis of biopsy, performed in 19 cases, showed that the main constituent of the deposits in all cases was the presence of peptides belonging to the constant region of the immunoglobulin kappa chain. A lymphoplasmocytic infiltrate was found in 13 cases. A search for B-cell clone in the lung was performed by PCR in 9 cases and revealed a clone in all patients.

Fiberoptic bronchoscopy

Fiberoptic bronchoscopy was performed in 24 patients. The macroscopic appearance of the bronchial mucosa was inflammatory in 29% of patients, normal in 42%, showed bronchial distorsions in 12.5%, and bronchomalacia in 8%. Bronchial biopsies were performed in 11 cases, including 8 with immunohistochemical analysis (positive in 5), and 3 with proteomic analysis (positive in all 3 cases).

Baseline CT characteristics

The most frequent abnormalities were plurifocal and sometimes extensive lung cysts (100%) and cystic bronchiectasis (77%). Cysts were bilateral and of regular shape and were characterised by internal septation (73%), bronchovascular topography (77%), and thin walls (Supplement Figure S 3 ). There was a wide variation in cyst size; the largest cysts were found abutting the pleura (Table  2 ). The patient population was then split according to whether patients presented with a cystic, bronchiectasis, or mixed CT pattern. FEV1 was significantly lower, and airflow obstruction was significantly more severe in the cystic pattern compared to the bronchiectasis pattern (Table  3 ).

Extrapulmonary manifestations

In four cases, LC deposits were found in salivary glands, one case being associated with primary Sjögren syndrome. Kidney tissue was available in three cases and no deposit was found. Interventricular septum thickening on cardiac ultrasonography was found in none of the cases. No patient had congestive heart failure. Left ventricular ejection fraction was preserved in all cases, and diastolic dysfunction was absent. Low voltage was not present on electrocardiograms. Right heart catheterisation was performed in 11 patients (Supplement Table S 1 ).

Lung function and CT follow-up

Follow-up data were available for FEV1 in 26 patients and for DLCO in 17 patients. The median duration of lung function follow-up was 75 (2–180) months. The median annual overall FEV1 decline was 127 ml/year (2.2 – 877), and the median DLCO annual decline was 4.3%/year (1.9 – 8). Imaging follow-up was available for 16 patients with a median interval between the first and last chest CT of 62 (7–139) months. Cysts increased in size in 13 patients and in number in ten patients (Fig.  1 ). The number of bronchiectases increased in nine patients.

Long-term change in chest CT features in 3 patients showing 3 patterns. A and B CT scan at baseline and after 8 years in a patient with diffuse cystic bronchiectasis. C and D CT scan at baseline and after 1 year in a patient with regular round cysts of various sizes. E and F CT scan at baseline in a patient with micronodules and interlobular reticulation, and 7 years later with multiple cysts and ground glass attenuation

Nonpecific treatment left to the discretion of each investigator included inhaled glucocorticoids ( n  = 16), long-acting beta-agonists ( n  = 15), long-acting muscarinic antagonist ( n  = 6), long-term macrolide treatment ( n  = 9). In 16 cases, a treatment was prescribed to attempt treating the disease by targeting the underlying production of LC. In all cases except 4, the first line of chemotherapy was different for each patient, varying according to centres (Supplementary figure S 4 ).

Among the 16 patients treated, ten had evaluable measurements of serum-free LC before and after systemic treatment. A normalisation or reduction > 90% of serum-free LC kappa was obtained only in three patients. Only eight patients had evaluable annual FEV1 before and after systemic treatment. The annual decline in FEV1 did not differ significantly between the pre-and post-treatment periods ( p  = 0.73; Supplementary Table S 2 ).

Long-term supplemental nasal oxygen was used in 19 patients (66%). Fifteen patients underwent double lung transplantation, with a median interval between diagnosis and lung transplantation of 5 years (1–11). In 4/15 cases, the diagnosis of LCDD was made before the transplantation. No patient requiring a lung transplant was excluded from receiving it due to contraindications and no patient died on the lung transplant waiting list.

Survival and prognostic factors

When comparing patients deceased or transplanted with those alive or not transplanted, there were significant differences in age at onset of symptoms, baseline FEV1% predicted, FEV1/FVC, and ∆FEV1 (Table  4 ).

Three patients died at the age of 45, 55, and 68 years, all of them due to progressive respiratory failure. The median transplant-free survival was 9 years (Fig.  2 ). There was no significant difference in transplant-free survival between men and women, between smokers and non-smokers, between treated and non-treated, or between cystic and bronchiectatic patterns. A rapid decline in FEV1, defined as ∆FEV1 > 127 ml/year (median value), was associated with an increased risk of death or transplantation ( p  = 0.005) (Fig.  2 ).

Kaplan–Meier estimates of transplant-free survival. A transplant-free survival in all patients. B Yellow and blue curves correspond to Kaplan Meier estimates of the transplant-free survival for patients with FEV1 decline greater or less than 127 ml/year ( P value for log rank test). C Yellow and blue curves correspond to Kaplan Meier estimates of the transplant-free survival for patients with “bronchiectasis pattern” and “cystic pattern”, respectively ( P value for log rank test)

The present cohort of diffuse pulmonary LCDD, which is the largest to date, shows a female predominance, an increase in serum free monoclonal kappa LC at diagnosis, and a predominance of thin-walled lung cysts and bronchectases on CT. Moreover, pulmonary LCDD appears as a progressive airflow obstruction associated with a poor prognosis and limited response to chemotherapy. Double lung transplantation should be considered as a curative option in this population, and patients should be referred early for transplantation.

Diffuse pulmonary LCDD localized to the lungs is less well described than other cystic lung diseases such as lymphangioleiomyomatosis or pulmonary Langerhans cell histiocytosis. In the patients’ files, the disease was often reported as “unclassifiable diffuse cystic lung disease”, “idiopathic diffuse bronchiectasis”, or “atypical emphysema” before LCDD was considered. The diagnosis is probably often missed since IF is rarely applied to lung biopsies by pulmonary pathologists and frozen material is rarely available, although it is considered the diagnostic method of choice. In these situations, mass spectrometry may confirm the diagnosis, but is not widely available. Paraffin IF was not performed in the present cohort but a prior study suggested that this technique is feasible and could rescue some difficult diagnoses [ 20 ]. The pathological diagnosis was based on the findings of videothoracoscopic lung biopsy, bronchial biopsy, and/or lung explant. Interestingly, bronchial biopsy tissue analysis was sufficient to confirm the diagnosis in a large proportion of the patients in whom the diagnosis was suspected, and in the cases where IF could be performed on frozen bronchial biopsies. Hence, physicians should be alerted to use adequate tissue fixation methods (i.e. frozen tissue) when a diagnosis of LCDD is considered.

Previous studies clearly demonstrated that diffuse pulmonary LCDD differs clinically from the systemic multivisceral form and from the pulmonary nodular form of the disease [ 21 ]. Unlike patients in two recent reports [ 22 , 23 ], the patients herein rarely had underlying autoimmune conditions, in particular primary Sjögren syndrome. Nodular pulmonary LCDD may be associated with Sjögren syndrome more often than the cystic presentation [ 24 ].

The present results indicate that young females more frequently present with respiratory manifestations of LCDD. The most common lung function abnormality at baseline was decreased DLCO, probably related to the damage induced by LC deposits along the alveolar-capillary membrane, as observed in lung amyloidosis [ 25 ]. Airflow obstruction defined by FEV1/FVC < 70% was also common.

The CT findings of the present study were relatively heterogeneous. In contrast to the findings of Sheard et al. [ 26 ], pulmonary involvement primarily consisted of varicose bronchiectasis without nodular infiltrates, except in one case. The coexistence (and possible communication [ 12 ]) of thin-walled bronchiectasis and cystic changes is somewhat characteristic of diffuse pulmonary LCDD when compared to other cystic lung diseases, in particular lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome. Cysts in pulmonary LCDD are regular in shape with a predominance of lower distribution [ 27 ]. During follow-up, the size and the number of bronchiectases and pulmonary cysts increased remarkably. However, in some cases, distinguishing these two patterns was not possible, with extensive emphysema-like changes in severe forms, and it is conceivable that both bronchiectases and cyst result from a common mechanisme of elastolysis. Noteworthy, the majority of the patients herein were current or ex-smokers, and it cannot be excluded that tobacco smoking may have played a role in pulmonary lesion formation.

Monoclonal gammopathy is the presence in the serum of a monoclonal immunoglobulin produced by a B-cell clone. This biological anomaly fits with the concept of monoclonal gammopathy of clinical significance, in which the clone induces severe organ damage [ 28 ]. Herein, the free LC ratio was abnormal in the vast majority of patients, making it a plausible screening tool. Nevertheless, the serum level of kappa LC at baseline was not associated with a greater probability of lung transplant or death. As shown by the plasmacytosis greater than 10% found in certain patients who underwent bone marrow biopsy or aspiration, although the association of LCDD with haematological malignancy is possible [ 13 , 29 ], the absence of bone marrow abnormality upon immunohistology should not exclude pulmonary LCDD. In such cases, LC may be produced within the lungs [ 17 ]. No evidence of extrapulmonary LC deposition was observed in the present cohort, except in accessory salivary glands. As a result, pulmonary LCDD may be considered in the appropriate context, even in the absence of kidney dysfunction or proteinuria.

During follow-up, inter-patient variability in FEV1 decline was observed, however, the decline in lung function was generally faster than that seen in chronic obstructive pulmonary disease [ 30 ] or in other multiple cystic lung diseases [ 31 , 32 , 33 ], and diffusion capacity was severely altered. Patients who required a lung transplantation had a higher rate of FEV1 decline than non-transplanted patients. Consequently, lung function surveillance at 6–12 months intervals is of paramount importance to assess disease progression and identify possible transplantation candidates, especially when ΔFEV1 > 127 ml/year.

There is no validated therapeutic strategy for LCDD localized to the lung. The main treatment approach is to target the synthesis of monoclonal proteins, using the same treatments as those employed in multiple myeloma. In the present cohort, various medications were used (rituximab, alkylating agents, proteasome inhibitor, dexamethasone, antimetabolite) targeting the underlying production of light chains, as well as autologous blood stem cell transplantation. Using an exploratory analysis, no change in the annual rate of FEV1 decline before and after treatment was observed, whereas improved renal function was reported in patients treated with melphalan and prednisone [ 34 ] or autologous stem cell transplantation for renal LCDD [ 35 ]. The fact that tissue damage induced by LC deposits is irreversible may explain the absence of clinical improvement despite serum LC titers that tended to decrease upon treatment. It remains to be determined whether treatments allowing LC serum levels to return to normal may slow disease progression. Lung volume reduction surgery might be considered as an alternative to chemotherapy in selected cases [ 18 ].

Lung transplantation is currently the main treatment option in patients with respiratory failure resulting from LCDD, with no reported recurrence in the transplanted lungs [ 17 ]. This is in line with the relatively long median lung transplant-free survival found herein. However, the present analysis showed that there was a significant difference in lung-transplant free survival according to FEV1 decline, underlying the possible need for some patients to undergo transplantation as early as possible. In contrast, kidney transplantation is not considered an option in end-stage renal disease, as further kidney damage cannot be prevented in the transplanted organ [ 36 ]. In case of cardiac LCDD, LC deposits were identified as early as 3 months after heart transplantation [ 37 ].

This study has several limitations, including the relatively small sample size and the retrospective design. Second, its multicentric nature represents a source of variability in pulmonary function test measurements. Third, the lack of standardised therapy may have contributed to the lack of significant treatment benefit observed on lung function decline.

In conclusion, in this cohort of patients with diffuse pulmonary LCDD, women were more commonly affected than men. Low DLCO was the most commonly observed lung function abnormality. Rapid annual FEV1 decline was associated with a greater risk of death or transplantation. Systemic haematologic treatment did not reduce the annual lung function decline. Prospective larger studies are eagerly awaited.

Availability of data and materials

Data are available upon request to the corresponding author.

Abbreviations

Computed tomography

Diffusing capacity for carbon monoxide

Transfer coefficient for the lung for carbon monoxide

Forced vital capacity

Forced expiratory volume in one second

Immunofluorescence

Light chain

• Light chain deposition disease

Arterial oxygen partial pressure

Total lung capacity

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Acknowledgements

We thank the patients for agreeing to participate in this study. The authors would like to thank R. LAVRUT (Lyon, France), M. RABANT (Paris, France) and R. DUBOIS (Lille, France) for histopathological contribution and pathology slides; V. LANDEL for manuscript preparation;

OrphaLung network (collaborators)

19 Yurdagül UZUNHAN, Avicenne hospital, APHP, Paris Nord university, Paris, France.

20 Stéphane JOUNEAU, Pontchaillou Hospital, Rennes, France.

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Authors and affiliations.

Hospices Civils de Lyon, Centre de Référence Coordinateur Des Maladies Pulmonaires Rares (OrphaLung), Hôpital Louis Pradel, Service de Pneumologie, 69677, Lyon, France

François Lestelle, Mouhamad Nasser & Vincent Cottin

Service de Radiologie Et de Radiologie Interventionnelle, Hôpital Universitaire de Lausanne, Université de Lausanne, Lausanne, Suisse

Catherine Beigelman & David Rotzinger

Hospices Civils de Lyon, Hôpital Louis Pradel, Service de Radiologie, Lyon 69677U1206, Université de Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS, UMR 5220, F‐69621, 7 Avenue Jean Capelle O, 69100, Villeurbanne, France

Salim Si-Mohamed

Centre de Référence Constitutif Des Maladies Pulmonaires Rares (OrphaLung), CHU Lille, Service de Pneumologie, Lille, France

Lidwine Wemeau

Centre de Compétence Des Maladies Pulmonaires Rares (OrphaLung), CHU Strasbourg, Service de Pneumologie, Strasbourg, France

Sandrine Hirschi

Centre de Compétence Des Maladies Pulmonaires Rares (OrphaLung), CHU Toulouse, Hôpital LarreyUniversité Paul Sabatier, Toulouse, France

Grégoire Prevot

Service de Pneumologie Et de Transplantation Pulmonaire, Hopital Foch, Suresnes, France

Antoine Roux

Service de Pneumologie B Et de Transplantation Pulmonaire, AP-HP, Hôpital Bichat Claude-Bernard, Inserm U1152, Paris, France

Vincent Bunel

Centre de Compétence Des Maladies Pulmonaires Rares (OrphaLung), CHU Nancy, Service de Pneumologie, Nancy, France

Emmanuel Gomez

Centre Hospitalier Bretagne Sud, Service de Pneumologie, Lorient, France

Laurent Sohier

Centre de Compétence Des Maladies Pulmonaires Rares (OrphaLung), CHU Rouen, Service de Pneumologie, Rouen, France

Helene Morisse Pradier

Service de Pneumologie Et Transplantation Pulmonaire, CHU Marseille Nord, Aix-Marseille Université Marseille, Assistance Publique-Hôpitaux de Marseille, Marseille, France

Martine Reynaud Gaubert

Centre de Compétence Des Maladies Pulmonaires Rares (OrphaLung), CHU Besançon, Service de Pneumologie, Besançon, France

Anne Gondouin

Service de Pneumologie, Centre Hospitalier Universitaire Vaudois, Lausanne, CH, Suisse

Romain Lazor

Hospices Civils de Lyon, Hôpital Louis Pradel, Service d’explorations Fonctionnelles Respiratoires, 69677, Lyon, France

Jean-Charles Glerant

Hospices Civils de Lyon, Hôpital Louis Pradel, Service d’Anatomopathologie, 69677, Lyon, France

Françoise Thivolet Bejui

CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Service d’anatomie Et Cytologie Pathologiques, Toulouse, France

Magali Colombat

UMR754, INRAE; Member of RespiFil and ERN-LUNG, Université, Claude Bernard Lyon 1, Lyon, France

Vincent Cottin

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• Yurdagül Uzunhan
•  & Stéphane Jouneau

Contributions

François Lestelle: conception of the work; acquisition, analysis, and interpretation of data for the work; AND Drafting the work; AND Final approval of the version to be published; AND Agreement to be accountable for all aspects of the work. Catherine Beigelman: data acquisition and interpretation, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. David Rotzinger: data acquisition and interpretation, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Salim Si-Mohamed: data acquisition and interpretation, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Mouhamad Nasser: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Lidwine Wemeau: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Sandrine Hirschi: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Grégoire Prevot: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Antoine Roux: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Vincent Bunel: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Emmanuel Gomez: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Laurent Sohier: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Helene Morisse Pradier: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Martine Reynaud Gaubert: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Anne Gondouin: data acquisition and interpretation, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Romain Lazor: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Jean-Charles Glerant: data interpretation, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Françoise Thivolet Bejui: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Magali Colombat: data acquisition, AND revising of manuscript, AND approval of final version, AND agreement to be accountable of the work. Vincent Cottin (guarantor): conception and design of the work; analysis, and interpretation of data for the work; AND Drafting and revising the work; AND Final approval of the version to be published; AND Agreement to be accountable for all aspects of the work.

Corresponding author

Correspondence to Vincent Cottin .

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Ethics approval and consent to participate.

This study was conducted with respect to the Declaration of Helsinki. It was approved by the ethics committee of the Hospices Civils de Lyon and was registered with the national data protection agency (Commission Nationale de l’Informatique et des Libertés, number 20–075). According to the legislation in place at the time of the study, informed consent signature was waived, but each patient was informed by a written letter and could object to the use of their personal data.

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The authors declare no competing interests.

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Lestelle, F., Beigelman, C., Rotzinger, D. et al. Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease. Respir Res 25 , 159 (2024). https://doi.org/10.1186/s12931-024-02798-y

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Received : 18 October 2023

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Published : 10 April 2024

DOI : https://doi.org/10.1186/s12931-024-02798-y

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